Molecule Information

General Information of the Molecule (ID: Mol00939)

• Name: DNA-directed RNA polymerase subunit beta (RPOB) ,Staphylococcus aureus
• Synonyms: RNAP subunit beta; RNA polymerase subunit beta; Transcriptase subunit beta; SAOUHSC_00524
• Molecule Type: Protein
• Gene Name: rpoB
• Gene ID: 3920377
• Sequence:
  MAGQVVQYGRHRKRRNYARISEVLELPNLIEIQTKSYEWFLREGLIEMFRDISPIEDFTG
  NLSLEFVDYRLGEPKYDLEESKNRDATYAAPLRVKVRLIIKETGEVKEQEVFMGDFPLMT
  DTGTFVINGAERVIVSQLVRSPSVYFNEKIDKNGRENYDATIIPNRGAWLEYETDAKDVV
  YVRIDRTRKLPLTVLLRALGFSSDQEIVDLLGDNEYLRNTLEKDGTENTEQALLEIYERL
  RPGEPPTVENAKSLLYSRFFDPKRYDLASVGRYKTNKKLHLKHRLFNQKLAEPIVNTETG
  EIVVEEGTVLDRRKIDEIMDVLESNANSEVFELHGSVIDEPVEIQSIKVYVPNDDEGRTT
  TVIGNAFPDSEVKCITPADIIASMSYFFNLLSGIGYTDDIDHLGNRRLRSVGELLQNQFR
  IGLSRMERVVRERMSIQDTESITPQQLINIRPVIASIKEFFGSSQLSQFMDQANPLAELT
  HKRRLSALGPGGLTRERAQMEVRDVHYSHYGRMCPIETPEGPNIGLINSLSSYARVNEFG
  FIETPYRKVDLDTHAITDQIDYLTADEEDSYVVAQANSKLDENGRFMDDEVVCRFRGNNT
  VMAKEKMDYMDVSPKQVVSAATACIPFLENDDSNRALMGANMQRQAVPLMNPEAPFVGTG
  MEHVAARDSGAAITAKHRGRVEHVESNEILVRRLVEENGVEHEGELDRYPLAKFKRSNSG
  TCYNQRPIVAVGDVVEYNEILADGPSMELGEMALGRNVVVGFMTWDGYNYEDAVIMSERL
  VKDDVYTSIHIEEYESEARDTKLGPEEITRDIPNVSESALKNLDDRGIVYIGAEVKDGDI
  LVGKVTPKGVTELTAEERLLHAIFGEKAREVRDTSLRVPHGAGGIVLDVKVFNREEGDDT
  LSPGVNQLVRVYIVQKRKIHVGDKMCGRHGNKGVISKIVPEEDMPYLPDGRPIDIMLNPL
  GVPSRMNIGQVLELHLGMAAKNLGIHVASPVFDGANDDDVWSTIEEAGMARDGKTVLYDG
  RTGEPFDNRISVGVMYMLKLAHMVDDKLHARSTGPYSLVTQQPLGGKAQFGGQRFGEMEV
  WALEAYGAAYTLQEILTYKSDDTVGRVKTYEAIVKGENISRPSVPESFRVLMKELQSLGL
  DVKVMDEQDNEIEMTDVDDDDVVERKVDLQQNDAPETQKEVTD
• Function: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
• Uniprot ID: RPOB_STAA8

Kingdom: N.A.
Phylum: Firmicutes
Class: Bacilli
Order: Bacillales
Family: Staphylococcaceae
Genus: Staphylococcus
Species: Staphylococcus aureus

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Rifabutin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.H481N
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.A473T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.Q465R
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.L466S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.Q468K
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.D471Y
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.A477T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.I527M
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.S529L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.H481N+p.L466S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.H481N+p.S529L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.H481N+p.I527M
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.H481N+p.S529L+p.Q465R
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.H481N+p.A473T+p.A477T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifabutin
• Molecule Alteration: Missense mutation; p.D471Y+p.S486L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Rifampin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.H481N
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.A473T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.Q465R
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.L466S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.Q468K
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.D471Y
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.A477T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.I527M
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.S529L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.H481N+p.L466S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.H481N+p.S529L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.H481N+p.I527M
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.H481N+p.S529L+p.Q465R
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.H481N+p.A473T+p.A477T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifampin
• Molecule Alteration: Missense mutation; p.D471Y+p.S486L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Rifapentine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.A473T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.Q465R
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.L466S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.Q468K
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.D471Y
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.A477T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.I527M
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.S529L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.H481N+p.L466S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.H481N+p.S529L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.H481N+p.I527M
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.H481N+p.S529L+p.Q465R
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.H481N+p.A473T+p.A477T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

Disease Class: Staphylococcus aureus infection [1]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Rifapentine
• Molecule Alteration: Missense mutation; p.D471Y+p.S486L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus strain T109; 1280
• In Vitro Model: Staphylococcus aureus strain T112; 1280
• In Vitro Model: Staphylococcus aureus strain T113; 1280
• In Vitro Model: Staphylococcus aureus strain T115; 1280
• In Vitro Model: Staphylococcus aureus strain T118; 1280
• In Vitro Model: Staphylococcus aureus strain T124; 1280
• In Vitro Model: Staphylococcus aureus strain T161; 1280
• In Vitro Model: Staphylococcus aureus strain T166; 1280
• In Vitro Model: Staphylococcus aureus strain T20; 1280
• In Vitro Model: Staphylococcus aureus strain T211; 1280
• In Vitro Model: Staphylococcus aureus strain T212; 1280
• In Vitro Model: Staphylococcus aureus strain T23; 1280
• In Vitro Model: Staphylococcus aureus strain T236; 1280
• In Vitro Model: Staphylococcus aureus strain T23aa; 1280
• In Vitro Model: Staphylococcus aureus strain T23aac; 1280
• In Vitro Model: Staphylococcus aureus strain T23bb; 1280
• In Vitro Model: Staphylococcus aureus strain T248; 1280
• In Vitro Model: Staphylococcus aureus strain T249; 1280
• In Vitro Model: Staphylococcus aureus strain T25; 1280
• In Vitro Model: Staphylococcus aureus strain T250; 1280
• In Vitro Model: Staphylococcus aureus strain T262; 1280
• In Vitro Model: Staphylococcus aureus strain T264; 1280
• In Vitro Model: Staphylococcus aureus strain T295; 1280
• In Vitro Model: Staphylococcus aureus strain T296; 1280
• In Vitro Model: Staphylococcus aureus strain T297; 1280
• In Vitro Model: Staphylococcus aureus strain T36; 1280
• In Vitro Model: Staphylococcus aureus strain T38; 1280
• In Vitro Model: Staphylococcus aureus strain T382; 1280
• In Vitro Model: Staphylococcus aureus strain T38aa; 1280
• In Vitro Model: Staphylococcus aureus strain T38bb; 1280
• In Vitro Model: Staphylococcus aureus strain T397; 1280
• In Vitro Model: Staphylococcus aureus strain T398; 1280
• In Vitro Model: Staphylococcus aureus strain T399; 1280
• In Vitro Model: Staphylococcus aureus strain T4; 1280
• In Vitro Model: Staphylococcus aureus strain T400; 1280
• In Vitro Model: Staphylococcus aureus strain T401; 1280
• In Vitro Model: Staphylococcus aureus strain T402; 1280
• In Vitro Model: Staphylococcus aureus strain T403; 1280
• In Vitro Model: Staphylococcus aureus strain T404; 1280
• In Vitro Model: Staphylococcus aureus strain T46; 1280
• In Vitro Model: Staphylococcus aureus strain T59; 1280
• In Vitro Model: Staphylococcus aureus strain T66; 1280
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Twelve mutational changes at 10 positions were identified, with 473Ala-Thr representing a new mutation site. New amino acid substitutions, 465Gln-Arg, 466Leu-Ser, 468Gln-Lys, and 477Ala-Thr in cluster I and 527Ile-Met and 529Ser-Leu in cluster II, were described, thereby emphasizing the high variability of these amino acid positions. Codon 481 was mutated on 32 separate occasions, which indicates a central role of this amino acid. All in vivo isolates that demonstrated two or three amino acid changes exhibited high-level resistance. Interestingly enough, all of these isolates showed the mutational change 481His-Asn, which is capable of conferring low-level resistance on its own, thereby indicating a two-step resistance mechanism in vivo to high-level resistance within these isolates. High-level resistance in vivo, however, was not demonstrated to occur through multiple mutations alone. The single amino acid substitution 468Gln-Lys also causes high-level resistance.

References

• Ref 1: Molecular characterization of rpoB mutations conferring cross-resistance to rifamycins on methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1999 Nov;43(11):2813-6. doi: 10.1128/AAC.43.11.2813.