| Autor: |
McNicholas, Paul M., Mann, Paul A., Najarian, David J., Miesel, Lynn, Hare, Roberta S., Black, Todd A. |
| Zdroj: |
Antimicrobial Agents and Chemotherapy; January 2001, Vol. 45 Issue: 1 p79-83, 5p |
| Abstrakt: |
ABSTRACTChemical mutagenesis of Staphylococcus aureusRN450 generated two strains that displayed a stable reduction (30- to 60-fold) in susceptibility to evernimicin. Cell-free translation reactions demonstrated that the resistance determinant was located in the ribosomal fraction. Compared to ribosomes isolated from a wild-type strain, ribosomes from the mutant strains displayed an 8- to 10-fold reduction in affinity for [14C]evernimicin. In contrast, the mutants displayed no alteration in either binding affinity or in vitro susceptibility to erythromycin. Exponential cultures of the mutant strains accumulated significantly less [14C]evernimicin than the wild-type strain, suggesting that accumulation is dependent on the high affinity that evernimicin displays for its binding site. Sequencing rplP(encodes ribosomal protein L16) in the mutant strains revealed a single base change in each strain, which resulted in a substitution of either cysteine or histidine for arginine at residue 51. Introduction of a multicopy plasmid carrying wild-type rplPinto the mutant strains restored sensitivity to evernimicin, confirming that the alterations in rplPwere responsible for the change in susceptibility. Overexpression of the mutant alleles in S. aureusRN450 had no effect on susceptibility to evernimicin, demonstrating that susceptibility is dominant over resistance. |
| Databáze: |
Supplemental Index |
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