1887

Abstract

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 strain H37Rv and the model organism strain PM274. The mutants PM638 (Δ) and PM759 (Δ) 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 mutant had no detectable -lactamase activity, while the mutant had a residual type 1 -lactamase activity. We identified a gene, , encoding a putative cephalosporinase in . A double -lactamase mutant of , PM976 (ΔΔ : : ), had no detectable -lactamase activity, but its susceptibility to -lactam antibiotics was not significantly different from that of the Δ 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.

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2005-02-01
2019-09-19
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