Drug Information

Drug (ID: DG00190) and It's Reported Resistant Information

• Name: Rifapentine
• Synonyms: RIFAPENTINE; Rifapentina; Rifapentinum; Cyclopentylrifampicin; Rifamycin AF/ACPP; Antibiotic DL 473IT; KTC 1; 61379-65-5; MDL 473; DRG-0283; DL 473; R-773; R 77-3; 3-(N-(4-Cyclopentyl-1-piperazinyl)formimidoyl)rifamycin; 3-(4-Cyclopentyl-1-piperazinyl)iminomethylrifamycin SV; 3-(((4-Cyclopentyl-1-piperazinyl)imino)methyl)rifamycin; Rifapentin,(S); NCGC00167431-01; ZINC169621228; NCGC00167431-03; AN-15578; RPE
• Indication:
  In total 2 Indication(s)
  HIV-infected patients with tuberculosis [ICD-11: 1B10-1B14]; Approved; [1]
  Retinopathy [ICD-11: 9B71]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [2]
  Staphylococcus meningitis [ICD-11: 1B54]; [1]
• Target: DNA-directed RNA polymerase (RNAP); NOUNIPROTAC; [1]
• Formula: C47H64N4O12
• IsoSMILES: C[C@H]1/C=C/C=C(\\C(=O)NC2=C(C(=C3C(=C2O)C(=C(C4=C3C(=O)[C@](O4)(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)C)O)O)/C=N/N5CCN(CC5)C6CCCC6)/C
• InChI: 1S/C47H64N4O12/c1-24-13-12-14-25(2)46(59)49-37-32(23-48-51-20-18-50(19-21-51)31-15-10-11-16-31)41(56)34-35(42(37)57)40(55)29(6)44-36(34)45(58)47(8,63-44)61-22-17-33(60-9)26(3)43(62-30(7)52)28(5)39(54)27(4)38(24)53/h12-14,17,22-24,26-28,31,33,38-39,43,53-57H,10-11,15-16,18-21H2,1-9H3,(H,49,59)/b13-12+,22-17+,25-14-,48-23+/t24-,26+,27+,28+,33-,38-,39+,43+,47-/m0/s1
• InChIKey: WDZCUPBHRAEYDL-GZAUEHORSA-N
• PubChem CID: 135403821
• ChEBI ID: CHEBI:45304
• TTD Drug ID: D0G9IU
• INTEDE ID: DR1421
• DrugBank ID: DB01201

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

Bacterial infection [ICD-11: 1A00-1C4Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Protein TetT (TETT) [2]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Streptococcus pyogenes infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain TG1; 562
• In Vitro Model: Streptococcus agalactiae strain B130; 1311
• In Vitro Model: Streptococcus anginosus strain MG16; 1328
• In Vitro Model: Streptococcus anginosus strain MG23; 1328
• In Vitro Model: Streptococcus anginosus strain MG32; 1328
• In Vitro Model: Streptococcus bovis strain D135; 1335
• In Vitro Model: Streptococcus bovis strain D295; 1335
• In Vitro Model: Streptococcus equisimilis strain C94; 119602
• In Vitro Model: Streptococcus equisimilis strain C95; 119602
• In Vitro Model: Streptococcus equisimilis strain C96; 119602
• In Vitro Model: Streptococcus pyogenes strain A498; 1314
• In Vitro Model: Streptococcus sp. strain G59; 1306
• Experiment for Molecule Alteration: PCR
• Mechanism Description: The gene tet(T) was isolated from Streptococcus pyogenes A498, and the nucleotide sequence that was necessary and sufficient for the expression of tetracycline resistance in Escherichia coli was determined. The deduced Tet(T) protein consists of 651 amino acids. A phylogenetic analysis revealed that Tet T represents a novel branching order among the Tet determinants so far described.

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.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.
• Ref 2: New tetracycline resistance determinants coding for ribosomal protection in streptococci and nucleotide sequence of tet(T) isolated from Streptococcus pyogenes A498. Antimicrob Agents Chemother. 1997 Jan;41(1):112-6. doi: 10.1128/AAC.41.1.112.