A Novel Gene,erm(41), Confers Inducible Macrolide Resistance to Clinical Isolates ofMycobacterium abscessusbut Is Absent fromMycobacterium chelonae

Top Cited Papers
Publisher Website
Google Scholar
Abstract
Mycobacterium abscessusinfections tend to respond poorly to macrolide-based chemotherapy, even though the organisms appear to be susceptible to clarithromycin. Circumstantial evidence suggested that at least someM. abscessusisolates might be inducibly resistant to macrolides. Thus, the purpose of this study was to investigate the macrolide phenotype ofM. abscessusclinical isolates. Inducible resistance to clarithromycin (MIC > 32 μg/ml) was found for 7 of 10 clinical isolates ofM. abscessuspreviously considered susceptible; the remaining 3 isolates were deemed to be susceptible (MIC ≤ 0.5 μg/ml). Inducible resistance was conferred by a novelermgene,erm(41), which was present in all 10 isolates and in an isolate ofMycobacterium bolletii(M. abscessustype II). However, theerm(41) alleles were nonfunctional in the three susceptibleM. abscessusisolates. No evidence oferm(41) was found inMycobacterium chelonae, and an isolate ofMycobacterium massilienseappeared to be anerm(41) deletion mutant. Expression oferm(41) inM. abscessusconferred resistance to clarithromycin and erythromycin and the ketolide HMR3004. However, this species was found to be intrinsically resistant, independent oferm(41), to clindamycin, quinupristin (streptogramin B), and telithromycin. The ability to confer resistance to clindamycin and telithromycin, but not quinupristin, was demonstrated by expressingerm(41) inMaycobacterium smegmatis. Exposure ofM. abscessusto the macrolide-lincosamide-streptogramin B-ketolide agents increased the levels oferm(41) mRNA 23- to 250-fold within 24 h. The inducible macrolide resistance phenotype of someM. abscessusisolates may explain the lack of efficacy of macrolide-based chemotherapy against this organism.