{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:36:40Z","timestamp":1789616200412,"version":"build-2803163510"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T00:00:00Z","timestamp":1474588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["104785\/Z\/14\/Z"],"award-info":[{"award-number":["104785\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","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":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The increasing global prevalence of drug resistance among many leading human pathogens necessitates both the development of antibiotics with novel mechanisms of action and a better understanding of the physiological activities of preexisting clinically effective drugs. Inhibition of peptidoglycan (PG) biosynthesis and cross-linking has traditionally enjoyed immense success as an antibiotic target in multiple bacterial pathogens, except in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis<\/jats:named-content>\n            , where it has so far been underexploited.\n            <jats:sc>d<\/jats:sc>\n            -Cycloserine, a clinically approved antituberculosis therapeutic, inhibits enzymes within the\n            <jats:sc>d<\/jats:sc>\n            -alanine subbranch of the PG-biosynthetic pathway and has been a focus in our laboratory for understanding peptidoglycan biosynthesis inhibition and for drug development in studies of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            . During our studies on alternative inhibitors of the\n            <jats:sc>d<\/jats:sc>\n            -alanine pathway, we discovered that the canonical alanine racemase (Alr) inhibitor \u03b2-chloro\u2013\n            <jats:sc>d<\/jats:sc>\n            -alanine (BCDA) is a very poor inhibitor of recombinant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            Alr, despite having potent antituberculosis activity. Through a combination of enzymology, microbiology, metabolomics, and proteomics, we show here that BCDA does not inhibit the\n            <jats:sc>d<\/jats:sc>\n            -alanine pathway in intact cells, consistent with its poor\n            <jats:italic>in vitro<\/jats:italic>\n            activity, and that it is instead a mechanism-based inactivator of glutamate racemase (MurI), an upstream enzyme in the same early stage of PG biosynthesis. This is the first report to our knowledge of inhibition of MurI in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            and thus provides a valuable tool for studying this essential and enigmatic enzyme and a starting point for future MurI-targeted antibacterial development.\n          <\/jats:p>","DOI":"10.1128\/aac.01249-16","type":"journal-article","created":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T03:04:34Z","timestamp":1470107074000},"page":"6091-6099","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"title":["Glutamate Racemase Is the Primary Target of \u03b2-Chloro-\n            <scp>d<\/scp>\n            -Alanine in Mycobacterium tuberculosis"],"prefix":"10.1128","volume":"60","author":[{"given":"Gareth A.","family":"Prosser","sequence":"first","affiliation":[{"name":"Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Rodenburg","sequence":"additional","affiliation":[{"name":"Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hania","family":"Khoury","sequence":"additional","affiliation":[{"name":"Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesira","family":"de Chiara","sequence":"additional","affiliation":[{"name":"Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, London, United 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