Journal
EMBO JOURNAL
Volume 28, Issue 6, Pages 736-744Publisher
WILEY
DOI: 10.1038/emboj.2009.17
Keywords
efflux pump; erythromycin; masking; mutation; resistance; ribosome
Categories
Funding
- Swedish Research Council
- NIH [GM70768]
- Wellcome Trust [070210/Z/03/Z]
- Estonian Science Foundation [6768]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available