TABLE 1

Selection and characterization of S. aureus SH1000 mutants resistant to aaRS inhibitors

StrainCompetitive fitnessaMutation frequency of resistance toa:
MupirocinREP8839GSK2251052
SH10001(5.3 ± 0.6) × 10−8(7.1 ± 0.2) × 10−7(2.5 ± 0.5) × 10−7
SH1000 IleRSV588F0.93 ± 0.04NDb(7.3 ± 0.1) × 10−7(2.7 ± 0.3) × 10−7
SH1000 IleRSV631F0.98 ± 0.04ND(7.9 ± 0.5) × 10−7(3.1 ± 0.5) × 10−7
SH1000 MetRSI57N0.90 ± 0.08(7.8 ± 0.4) × 10−8ND(3.1 ± 0.1) × 10−7
SH1000 MetRSV242F0.87 ± 0.02(7.3 ± 0.1) × 10−8ND(3.4 ± 0.5) × 10−7
SH1000 LeuRSG303V0.86 ± 0.02(7.4 ± 0.4) × 10−8(7.6 ± 0.4) × 10−7ND
SH1000 LeuRSD346N0.91 ± 0.01(7.8 ± 0.3) × 10−8(7.2 ± 0.1) × 10−7ND
SH1000 IleRSV588F MetRSV242F0.62 ± 0.02NDNDND
SH1000 IleRSV588F LeuRSG303V0.68 ± 0.07NDNDND
SH1000 IleRSV631F MetRSV242F0.58 ± 0.04NDNDND
SH1000 IleRSV631F LeuRSG303V0.65 ± 0.01NDNDND
SH1000 MetRSI57N LeuRSG303V0.65 ± 0.04NDNDND
SH1000 MetRSV242F LeuRSD346N0.61 ± 0.01NDNDND
SH1000 MetRSI57N IleRSV588F0.64 ± 0.09NDNDND
SH1000 LeuRSG303V MetRSV242F0.69 ± 0.02NDNDND
SH1000 LeuRSD346N IleRSV588F0.66 ± 0.05NDNDND
  • a Results are means ± SD of at least three independent experiments.

  • b ND, not determined.