{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:11:23Z","timestamp":1791277883455,"version":"4.1.0"},"reference-count":43,"publisher":"Microbiology Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,2,1]]},"abstract":"<jats:p>Mycobacteria produce <jats:italic>\u03b2<\/jats:italic>-lactamases and are intrinsically resistant to <jats:italic>\u03b2<\/jats:italic>-lactam antibiotics. In addition to the <jats:italic>\u03b2<\/jats:italic>-lactamases, cell envelope permeability and variations in certain peptidoglycan biosynthetic enzymes are believed to contribute to <jats:italic>\u03b2<\/jats:italic>-lactam resistance in these organisms. To allow the study of these additional mechanisms, mutants of the major <jats:italic>\u03b2<\/jats:italic>-lactamases, BlaC and BlaS, were generated in the pathogenic <jats:italic>Mycobacterium tuberculosis<\/jats:italic> strain H37Rv and the model organism <jats:italic>Mycobacterium smegmatis<\/jats:italic> strain PM274. The mutants <jats:italic>M. tuberculosis<\/jats:italic> PM638 (\u0394<jats:italic>blaC1<\/jats:italic>) and <jats:italic>M. smegmatis<\/jats:italic> PM759 (\u0394<jats:italic>blaS1<\/jats:italic>) showed an increase in susceptibility to <jats:italic>\u03b2<\/jats:italic>-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 <jats:italic>\u03b2<\/jats:italic>-lactam antibiotics was affected most, compared to the cephalosporin-type <jats:italic>\u03b2<\/jats:italic>-lactam antibiotics. The <jats:italic>M. tuberculosis<\/jats:italic> mutant had no detectable <jats:italic>\u03b2<\/jats:italic>-lactamase activity, while the <jats:italic>M. smegmatis<\/jats:italic> mutant had a residual type 1 <jats:italic>\u03b2<\/jats:italic>-lactamase activity. We identified a gene, <jats:italic>blaE<\/jats:italic>, encoding a putative cephalosporinase in <jats:italic>M. smegmatis<\/jats:italic>. A double <jats:italic>\u03b2<\/jats:italic>-lactamase mutant of <jats:italic>M. smegmatis<\/jats:italic>, PM976 (\u0394<jats:italic>blaS1<\/jats:italic>\u0394<jats:italic>blaE<\/jats:italic>\u200a:\u200a:\u200a<jats:italic>res<\/jats:italic>), had no detectable <jats:italic>\u03b2<\/jats:italic>-lactamase activity, but its susceptibility to <jats:italic>\u03b2<\/jats:italic>-lactam antibiotics was not significantly different from that of the \u0394<jats:italic>blaS1<\/jats:italic> parental strain, PM759. The mutants generated in this study will help determine the contribution of other <jats:italic>\u03b2<\/jats:italic>-lactam resistance mechanisms in addition to serving as tools to study the biology of peptidoglycan biosynthesis in these organisms.<\/jats:p>","DOI":"10.1099\/mic.0.27629-0","type":"journal-article","created":{"date-parts":[[2005,2,7]],"date-time":"2005-02-07T23:28:34Z","timestamp":1107818914000},"page":"521-532","source":"Crossref","is-referenced-by-count":200,"title":["Genetic analysis of the \u03b2-lactamases of Mycobacterium tuberculosis and Mycobacterium smegmatis and susceptibility to \u03b2-lactam antibiotics"],"prefix":"10.1099","volume":"151","author":[{"given":"Anthony R.","family":"Flores","sequence":"first","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry and Department of Microbiology and Immunology, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M.","family":"Parsons","sequence":"additional","affiliation":[{"name":"The Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S.","family":"Pavelka,","sequence":"additional","affiliation":[{"name":"University of Rochester School of Medicine and Dentistry and Department of Microbiology and Immunology, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1098\/rstb.1980.0049","article-title":"The structure of \u03b2-lactamases","volume":"289","author":"Ambler","year":"1980","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"R2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1042\/bj2760269","article-title":"A standard numbering scheme for the class A \u03b2-lactamases","volume":"276","author":"Ambler","year":"1991","journal-title":"Biochem J"},{"key":"R3","first-page":"557","article-title":"Characterization of a \u03b2-lactamase from Mycobacterium smegmatis SN2","volume":"43","author":"Basu","year":"1997","journal-title":"Biochem Mol Biol Int"},{"key":"R4","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1128\/AAC.39.6.1211","article-title":"A functional classification scheme for \u03b2-lactamases and its correlation with molecular structure","volume":"39","author":"Bush","year":"1995","journal-title":"Antimicrob Agents Chemother"},{"key":"R5","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1128\/AAC.31.1.132","article-title":"In vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis, Mycobacterium avium, Mycobacterium fortuitum, and Mycobacterium chelonae to ticarcillin in combination with clavulanic acid","volume":"31","author":"Casal","year":"1987","journal-title":"Antimicrob Agents Chemother"},{"key":"R6","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1128\/AAC.39.12.2620","article-title":"Can penicillins and other \u03b2-lactam antibiotics be used to treat tuberculosis?","volume":"39","author":"Chambers","year":"1995","journal-title":"Antimicrob Agents Chemother"},{"key":"R7","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1086\/513945","article-title":"Activity of amoxicillin\/clavulanate in patients with tuberculosis","volume":"26","author":"Chambers","year":"1998","journal-title":"Clin Infect Dis"},{"key":"R8","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/31159","article-title":"& 39 other authors","volume":"393","author":"Cole","year":"1998","journal-title":"Nature"},{"key":"R9","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0378-1097(03)00502-0","article-title":"Extragenic suppression of the requirement for diaminopimelate in diaminopimelate auxotrophs of Mycobacterium smegmatis","volume":"225","author":"Consaul","year":"2003","journal-title":"FEMS Microbiol Lett"},{"key":"R10","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1128\/AAC.24.3.429","article-title":"In vitro activity of amoxicillin in combination with clavulanic acid against Mycobacterium tuberculosis","volume":"24","author":"Cynamon","year":"1983","journal-title":"Antimicrob Agents Chemother"},{"key":"R11","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1128\/AAC.19.1.205","article-title":"In vitro susceptibility of Mycobacterium fortuitum to cefoxitin","volume":"19","author":"Cynamon","year":"1981","journal-title":"Antimicrob Agents Chemother"},{"key":"R12","first-page":"677","article-title":"Consensus statement. 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