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Genetic analysis of the -lactamases of Mycobacterium tuberculosis and Mycobacterium smegmatis and susceptibility to -lactam antibiotics

¹ University of Rochester School of Medicine and Dentistry and Department of Microbiology and Immunology, Rochester, NY 14642, USA
² The Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA

Correspondence
Martin S. Pavelka, Jr
Martin_Pavelka{at}urmc.rochester.edu

Mycobacteria produce -lactamases and are intrinsically resistant to -lactam antibiotics. In addition to the -lactamases, cell envelope permeability and variations in certain peptidoglycan biosynthetic enzymes are believed to contribute to -lactam resistance in these organisms. To allow the study of these additional mechanisms, mutants of the major -lactamases, BlaC and BlaS, were generated in the pathogenic Mycobacterium tuberculosis strain H37Rv and the model organism Mycobacterium smegmatis strain PM274. The mutants M. tuberculosis PM638 (blaC1) and M. smegmatis PM759 (blaS1) showed an increase in susceptibility to -lactam antibiotics, as determined by disc diffusion and minimal inhibitory concentration (MIC) assays. The susceptibility of the mutants, as assayed by disc diffusion tests, to penicillin-type -lactam antibiotics was affected most, compared to the cephalosporin-type -lactam antibiotics. The M. tuberculosis mutant had no detectable -lactamase activity, while the M. smegmatis mutant had a residual type 1 -lactamase activity. We identified a gene, blaE, encoding a putative cephalosporinase in M. smegmatis. A double -lactamase mutant of M. smegmatis, PM976 (blaS1blaE : : res), had no detectable -lactamase activity, but its susceptibility to -lactam antibiotics was not significantly different from that of the blaS1 parental strain, PM759. The mutants generated in this study will help determine the contribution of other -lactam resistance mechanisms in addition to serving as tools to study the biology of peptidoglycan biosynthesis in these organisms.

The GenBank/EMBL/DDBJ accession numbers for the sequences reported in this paper are AY332268 and AY442183.

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