{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:10:28Z","timestamp":1791159028079,"version":"4.1.0"},"reference-count":0,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[1995,12,1]],"date-time":"1995-12-01T00:00:00Z","timestamp":817776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[1995,12]]},"abstract":"<jats:p>An increase in the number of tuberculosis cases caused by multiple-drug-resistant strains of Mycobacterium tuberculosis has stimulated search for new antituberculous agents. Beta-lactam antibiotics, traditionally regarded as ineffective against tuberculosis, merit consideration. Four major penicillin-binding proteins (PBPs) with approximate molecular sizes of 94, 82, 52, and 37 kDa were detected by fluorography of [3H]penicillin-radiolabeled membrane proteins prepared from M. tuberculosis H37Ra. The presence of membrane-associated beta-lactamase precluded the use of membranes for assaying the binding affinities of beta-lactam antibiotics. Therefore, ampicillin affinity chromatography was used to purify these four PBPs from crude membranes in order to assay the binding affinities of beta-lactam antibiotics. Ampicillin, amoxicillin, and imipenem, beta-lactam antibiotics previously reported to be active in vitro against M. tuberculosis, bound to M. tuberculosis PBPs at therapeutically achievable concentrations. Binding of the 94-, 82-, and 52-kDa PBPs, but not the 37-kDa PBP, was associated with antibacterial activity, suggesting that these PBPs are the critical targets. Studies of mycobacterial cell wall permeability, which was assayed with a panel of reference cephalosporins and penicillins with different charge positivities, indicated that the rate of penetration of beta-lactam antibiotics to the target PBPs could not account for resistance. Resistance could be reversed with the beta-lactamase inhibitors clavulanate or sulbactam or could be circumvented by the use of a beta-lactamase-stable drug, imipenem, indicating that mycobacterial beta-lactamase, probably in conjunction with slow penetration, is a major determinant of M. tuberculosis resistance to beta-lactam antibiotics. These findings confirm in vitro data that M. tuberculosis is susceptible to some beta-lactam antibiotics. Further evaluation of these drugs for the treatment of tuberculosis in animal models and in clinical trials is warranted.<\/jats:p>","DOI":"10.1128\/aac.39.12.2620","type":"journal-article","created":{"date-parts":[[2012,6,28]],"date-time":"2012-06-28T00:06:25Z","timestamp":1340841985000},"page":"2620-2624","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":167,"title":["Can penicillins and other beta-lactam antibiotics be used to treat tuberculosis?"],"prefix":"10.1128","volume":"39","author":[{"given":"H F","family":"Chambers","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California, San Francisco 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Moreau","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Yajko","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Miick","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Hackbarth","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Kocag\u00f6z","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W K","family":"Hadley","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Nikaido","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.39.12.2620","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.39.12.2620","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:00:58Z","timestamp":1645473658000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.39.12.2620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,12]]},"references-count":0,"journal-issue":{"issue":"12","published-print":{"date-parts":[[1995,12]]}},"alternative-id":["10.1128\/AAC.39.12.2620"],"URL":"https:\/\/doi.org\/10.1128\/aac.39.12.2620","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,12]]},"assertion":[{"value":"1995-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}