Affiliation:
1. Children's Hospital Los Angeles and University of Southern California, Los Angeles, California
Abstract
ABSTRACT
High-level, acquired macrolide resistance in mycobacteria is conferred by mutation within the 23S rRNA gene. However, several mycobacteria are naturally resistant to macrolides, including the
Mycobacterium smegmatis
group and
Mycobacterium tuberculosis
complex. Thus, the aim of this study was to characterize this resistance. Intrinsic macrolide resistance in
M. smegmatis
was inducible and showed cross-resistance to lincosamides but not to streptogramin B (i.e., ML resistance). A similar phenotype was found with
Mycobacterium microti
and macrolide-resistant
Mycobacterium fortuitum
. A search of the DNA sequence data for
M. smegmatis
strain mc
2
155 identified a novel
erm
gene,
erm
(38), and expression analysis showed that
erm
(38) RNA levels increased >10-fold after a 2-h incubation with macrolide. Inducible ML resistance was not expressed by an
erm
(38) knockout mutant, and complementation of this mutant with intact
erm
(38) in
trans
resulted in high-level ML resistance (e.g., clarithromycin MIC of >512 μg/ml). Thus, the results indicate that
erm
(38) confers the intrinsic ML resistance of
M. smegmatis
. Southern blot analysis with an
erm
(38)-specific probe indicated that a similar gene may be present in macrolide-resistant
M. fortuitum
. This finding, with the presence of the
erm
(37) gene (Rv1988) in the
M. tuberculosis
complex, suggests that such genes are widespread in mycobacteria with intrinsic macrolide resistance.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference27 articles.
1. Basic local alignment search tool
2. Belisle, J. T., and M. G. Sonnenberg. 1998. Isolation of genomic DNA from mycobacteria. Methods Mol. Biol.101:31-44.
3. Bosne-David, S., V. Barros, S. C. Verde, C. Portugal, and H. L. David. 2000. Intrinsic resistance of Mycobacterium tuberculosis to clarithromycin is effectively reversed by subinhibitory concentrations of cell wall inhibitors. J. Antimicrob. Chemother.46:391-395.
4. Brown B. A. J. M. Swenson and R. J. Wallace Jr. 1993. Broth microdilution MIC test for rapidly growing mycobacteria p. 5.11.1. In H. D. Isenberg (ed.) Clinical microbiology procedures handbook vol. 1. American Society for Microbiology Washington D.C.
5. Brown-Elliott, B. A., D. E. Griffith, and R. J. Wallace, Jr. 2002. Newly described or emerging human species of nontuberculous mycobacteria. Infect. Dis. Clin. North Am.16:187-220.
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