Drug Information

Drug (ID: DG00064) and It's Reported Resistant Information

• Name: Rifabutin
• Synonyms: Alfacid; Ansamycin; Ansatipin; Ansatipine; Assatipin; Mycobutin; RBT; Rifabutina; Rifabutine; Rifabutinum; Grunenthal Brand of Rifabutin; Kenfarma Brand of Rifabutin; Pfizer Brand of Rifabutin; Rifabutin Pfizer Brand; Rifabutina [Spanish]; Rifabutine [French]; Rifabutinum [Latin]; Antibiotic LM 427; LM 427; LM427; DRG-0085; LM-427; Mycobutin (TN); Rifabutin [USAN:BAN:INN]; Rifabutin (JAN/USP/INN); Mycobutin, Ansamycin, LM 427, Ansatipine, Rifabutin; (9S,12E,14S,15R,16S,17R,18R,19R,20S,21S,22E,24Z)-6,18,20-trihydroxy-1'-isobutyl-14-methoxy-7,9,15,17,19,21,25-heptamethyl-5,10,26-trioxo-3,5,9,10-tetrahydrospiro[9,4-(epoxypentadeca[1,11,13]trienoimino)furo[2',3':7,8]naphtho[1,2-d]imidazole-2,4'-piperidin; Spiro[9,4-(epoxypentadeca[1,11,13]trienimino)-2H-furo[2',3':7,8]naphth[1,2-d]imidazole-2,4'-piperidine]-5,10,26(3H,9H)-trione, 16-(acetyloxy)-6,18,20-trihydroxy-14-methoxy-7,9,15,17,19,21,25-heptameth; 1,4-Dihydro-1-deoxy-1',4-didehydro-5'-(2-methylpropyl)-1-oxorifamycin XIV; 4-Deoxo-3,4-(2-spiro(N-isobutyl-4-piperidyl)-2,5-dihydro-1H-imidazo)-rifamycin S; 4-N-isobutylspiropiperidylrifamycin S
• Indication:
  In total 2 Indication(s)
  HIV-infected patients with tuberculosis [ICD-11: 1B10-1B14]; Approved; [1]
  Mycobacterium infection [ICD-11: 1B10-1B21]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Staphylococcus meningitis [ICD-11: 1B54]; [1]
• Target: DNA-directed RNA polymerase (RNAP); NOUNIPROTAC; [1]
• Formula: C46H62N4O11
• IsoSMILES: C[C@H]1/C=C/C=C(\\C(=O)N=C2C(=C3C(=C4C2=NC5(N4)CCN(CC5)CC(C)C)C6=C(C(=C3O)C)O[C@@](C6=O)(O/C=C/[C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@@H]([C@H]1O)C)O)C)OC(=O)C)C)OC)C)O)/C
• InChI: 1S/C46H62N4O11/c1-22(2)21-50-18-16-46(17-19-50)48-34-31-32-39(54)28(8)42-33(31)43(56)45(10,61-42)59-20-15-30(58-11)25(5)41(60-29(9)51)27(7)38(53)26(6)37(52)23(3)13-12-14-24(4)44(57)47-36(40(32)55)35(34)49-46/h12-15,20,22-23,25-27,30,37-38,41,48,52-55H,16-19,21H2,1-11H3/b13-12+,20-15+,24-14-,47-36 /t23-,25+,26+,27+,30-,37-,38+,41+,45-/m0/s1
• InChIKey: ZWBTYMGEBZUQTK-PVLSIAFMSA-N
• PubChem CID: 135398743
• TTD Drug ID: D05CHI
• INTEDE ID: DR1418
• DrugBank ID: DB00615

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Staphylococcus meningitis [ICD-11: 1B54]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.H481N
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.A473T
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.Q465R
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.L466S
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.Q468K
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.D471Y
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.A477T
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.I527M
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.S529L
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.H481N+p.L466S
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.H481N+p.S529L
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.H481N+p.I527M
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.H481N+p.S529L+p.Q465R
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.H481N+p.A473T+p.A477T
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.

Key Molecule: DNA-directed RNA polymerase subunit beta (RPOB) [1]

• Molecule Alteration: Missense mutation; p.D471Y+p.S486L
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• 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.