TABLE 1 

Impact of MexY mutations on antimicrobial susceptibility of P. aeruginosaa

StrainPlasmidMexY mutationMIC (μg/ml)b
STRPARNEOAMIERYSPCCAMNORcCEFd
K767NoneWT3225632251251264NDeND
K3315NoneNone2840.5646464NDND
K3315pRK415None21640.56464320.51
K3315pCL10WT864815125123224
K3315pCL14G216D216NDND6464320.51
K3315pCL13R184H432NDND25625632NDND
K3315pCL11S16F432NDND25625632NDND
K3315pCL17A960T416NDND25625632NDND
K3315pCL15V339M4168f15122563221
K3315pCL12R166C432NDND2565123224
K3315pCL16P562S832NDND25651232NDND
K3315pCL19D133A41640.5256102432NDND
K3315pCL20D133S41640.5256102432NDND
K3315pCL18K79A81288g1512102432NDND
K3315pCL21Y613A41640.55122563222
  • a The antimicrobial susceptibility of P. aeruginosa ΔmexY strain K3315 carrying the indicated plasmids expressing wild-type (WT) MexY or MexY derivatives with the indicated amino acid substitutions is reported. Results for WT strain K767 and plasmid-free K3315 are provided for comparison purposes.

  • b MIC values lower than that measured for pCL10-carrying K3315 expressing WT MexY are bolded. MIC values higher than that measured for pCL10-carrying K3315 are italicized. STR, streptomycin; PAR, paromomycin; NEO, neomycin; AMI, amikacin; ERY, erythromycin; SPC, spectinomycin; CAM, chloramphenicol; NOR, norfloxacin; CEF, cefepime.

  • c NOR MICs were determined in the presence of 8 µg/ml chloramphenicol. The NOR MIC for all strains in the absence of chloramphenicol was 0.5 µg/ml.

  • d CEF MICs were determined in the presence of 8 µg/ml chloramphenicol. The CEF MIC determined in the absence of chloramphenicol was 1 (for pRK415 control and MexYG216D) or 2 (for MexYWT and its V339M, R166C, and Y613A variants) μg/ml.

  • e ND, not determined.

  • f At half the NEO MIC (4 µg/ml), MexYV339M-expressing K3315 grew reproducibly slower than K3315 expressing MexYWT (data not shown), indicating that the V339M mutation compromises neomycin resistance.

  • g At half the NEO MIC (4 µg/ml), MexYK79A-expressing K3315 grew reproducibly faster than K3315 expressing MexYWT (data not shown), indicating that the K79A mutation enhances neomycin resistance.