HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Flores, A. R. Articles by Pavelka,, M. S. Search for Related Content PubMed PubMed Citation Articles by Flores, A. R. Articles by Pavelka,, M. S., Jr Agricola Articles by Flores, A. R. Articles by Pavelka,, M. S.

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.

This article has been cited by other articles:

				J. A. McDonough, J. R. McCann, E. M. Tekippe, J. S. Silverman, N. W. Rigel, and M. Braunstein Identification of Functional Tat Signal Sequences in Mycobacterium tuberculosis Proteins J. Bacteriol., October 1, 2008; 190(19): 6428 - 6438. [Abstract] [Full Text] [PDF]

				O. Danilchanka, M. Pavlenok, and M. Niederweis Role of Porins for Uptake of Antibiotics by Mycobacterium smegmatis Antimicrob. Agents Chemother., September 1, 2008; 52(9): 3127 - 3134. [Abstract] [Full Text] [PDF]

				O. Danilchanka, C. Mailaender, and M. Niederweis Identification of a Novel Multidrug Efflux Pump of Mycobacterium tuberculosis Antimicrob. Agents Chemother., July 1, 2008; 52(7): 2503 - 2511. [Abstract] [Full Text] [PDF]

				E. C. Hett and E. J. Rubin Bacterial Growth and Cell Division: a Mycobacterial Perspective Microbiol. Mol. Biol. Rev., March 1, 2008; 72(1): 126 - 156. [Abstract] [Full Text] [PDF]

				J. R. McCann, J. A. McDonough, M. S. Pavelka, and M. Braunstein beta-Lactamase can function as a reporter of bacterial protein export during Mycobacterium tuberculosis infection of host cells Microbiology, October 1, 2007; 153(10): 3350 - 3359. [Abstract] [Full Text] [PDF]

				E. D. LoVullo, L. A. Sherrill, L. L. Perez, and M. S. Pavelka Jr Genetic tools for highly pathogenic Francisella tularensis subsp. tularensis. Microbiology, November 1, 2006; 152(Pt 11): 3425 - 3435. [Abstract] [Full Text] [PDF]

				F. Wang, C. Cassidy, and J. C. Sacchettini Crystal Structure and Activity Studies of the Mycobacterium tuberculosis {beta}-Lactamase Reveal Its Critical Role in Resistance to {beta}-Lactam Antibiotics. Antimicrob. Agents Chemother., August 1, 2006; 50(8): 2762 - 2771. [Abstract] [Full Text] [PDF]

				J. E. Posey, T. M. Shinnick, and F. D. Quinn Characterization of the Twin-Arginine Translocase Secretion System of Mycobacterium smegmatis J. Bacteriol., February 15, 2006; 188(4): 1332 - 1340. [Abstract] [Full Text] [PDF]

				J. A. McDonough, K. E. Hacker, A. R. Flores, M. S. Pavelka Jr, and M. Braunstein The Twin-Arginine Translocation Pathway of Mycobacterium smegmatis Is Functional and Required for the Export of Mycobacterial {beta}-Lactamases J. Bacteriol., November 15, 2005; 187(22): 7667 - 7679. [Abstract] [Full Text] [PDF]