Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Erythromycin resistance by L4/L22 mutations and resistance masking by drug efflux pump deficiency

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • معلومة اضافية
    • بيانات النشر:
      Wiley, 2009.
    • الموضوع:
      2009
    • نبذة مختصرة :
      We characterized the effects of classical erythromycin resistance mutations in ribosomal proteins L4 and L22 of the large ribosomal subunit on the kinetics of erythromycin binding. Our data are consistent with a mechanism in which the macrolide erythromycin enters and exits the ribosome through the nascent peptide exit tunnel, and suggest that these mutations both impair passive transport through the tunnel and distort the erythromycin-binding site. The growth-inhibitory action of erythromycin was characterized for bacterial populations with wild-type and L22-mutated ribosomes in drug efflux pump deficient and proficient backgrounds. The L22 mutation conferred reduced erythromycin susceptibility in the drug efflux pump proficient, but not deficient, background. This ‘masking' of drug resistance by pump deficiency was reproduced by modelling with input data from our biochemical experiments. We discuss the general principles behind the phenomenon of drug resistance ‘masking', and highlight its potential importance for slowing down the evolution of drug resistance among pathogens.
    • ISSN:
      1460-2075
      0261-4189
    • Rights:
      OPEN
    • الرقم المعرف:
      edsair.doi.dedup.....c0e87674e8960b24cc21d0207961be5e