{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:20:07Z","timestamp":1789820407526,"version":"4.0.1"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["DP2OD008459"],"award-info":[{"award-number":["DP2OD008459"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN272201400027C"],"award-info":[{"award-number":["HHSN272201400027C"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            \u03b2-Lactams are the most widely used antibacterials. Among \u03b2-lactams, carbapenems are considered the last line of defense against recalcitrant infections. As recent developments have prompted consideration of carbapenems for treatment of drug-resistant tuberculosis, it is only a matter of time before\n            <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n            strains resistant to these drugs will emerge. In the present study, we investigated the genetic basis that confers such resistance. To our surprise, instead of mutations in the known \u03b2-lactam targets, a single nucleotide polymorphism in the\n            <jats:italic>Rv2421c-Rv2422<\/jats:italic>\n            intergenic region was common among\n            <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n            mutants selected with meropenem or biapenem. We present data supporting the hypothesis that this locus harbors a previously unidentified gene that encodes a protein. This protein binds to \u03b2-lactams, slowly hydrolyzes the chromogenic \u03b2-lactam nitrocefin, and is inhibited by select penicillins and carbapenems and the \u03b2-lactamase inhibitor clavulanate. The mutation results in a W62R substitution that reduces the protein's nitrocefin-hydrolyzing activity and binding affinities for carbapenems.\n          <\/jats:p>","DOI":"10.1128\/aac.02234-16","type":"journal-article","created":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T02:30:27Z","timestamp":1484015427000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Mutation in an Unannotated Protein Confers Carbapenem Resistance in Mycobacterium tuberculosis"],"prefix":"10.1128","volume":"61","author":[{"given":"Pankaj","family":"Kumar","sequence":"first","affiliation":[{"name":"Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Taskforce To Study Resistance Emergence &amp; Antimicrobial Development Technology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Kaushik","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Taskforce To Study Resistance Emergence &amp; Antimicrobial Development Technology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drew T.","family":"Bell","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Taskforce To Study Resistance Emergence &amp; Antimicrobial Development Technology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varsha","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Taskforce To Study Resistance Emergence &amp; Antimicrobial Development Technology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Xia","sequence":"additional","affiliation":[{"name":"Argonne National Laboratory, Argonne, Illinois, USA"},{"name":"University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick L.","family":"Stevens","sequence":"additional","affiliation":[{"name":"Taskforce To Study Resistance Emergence &amp; Antimicrobial Development Technology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Argonne National Laboratory, Argonne, Illinois, USA"},{"name":"University of Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2214-0114","authenticated-orcid":false,"given":"Gyanu","family":"Lamichhane","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"},{"name":"Taskforce To Study Resistance Emergence &amp; Antimicrobial Development Technology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Global tuberculosis report","author":"WHO","year":"2015","unstructured":"WHO. 2015. Global tuberculosis report. 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Some common methods in mycobacterial genetics, p 313\u2013320. InHatfullGF JacobsWR Jr (ed), Molecular genetics of mycobacteria. 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