{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:52:21Z","timestamp":1791845541701,"version":"4.3.4"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"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":[[2012,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Active efflux of drugs mediated by efflux pumps that confer drug resistance is one of the mechanisms developed by bacteria to counter the adverse effects of antibiotics and chemicals. To understand these efflux mechanisms 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                    , we generated knockout (KO) mutants of four efflux pumps of the pathogen belonging to different classes. We measured the MICs and kill values of two different compound classes on the wild type (WT) and the efflux pump (EP) KO mutants in the presence and absence of the efflux inhibitors verapamil and\n                    <jats:sc>l<\/jats:sc>\n                    -phenylalanyl-\n                    <jats:sc>l<\/jats:sc>\n                    -arginyl-\u03b2-naphthylamide (PA\u03b2N). Among the pumps studied, the efflux pumps belonging to the ABC (ATP-binding cassette) class, encoded by\n                    <jats:italic>Rv1218c<\/jats:italic>\n                    , and the SMR (small multidrug resistance) class, encoded by\n                    <jats:italic>Rv3065<\/jats:italic>\n                    , appear to play important roles in mediating the efflux of different chemical classes and antibiotics. Efflux pumps encoded by\n                    <jats:italic>Rv0849<\/jats:italic>\n                    and\n                    <jats:italic>Rv1258c<\/jats:italic>\n                    also mediate the efflux of these compounds, but to a lesser extent. Increased killing is observed in WT\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                    cells by these compounds in the presence of either verapamil or PA\u03b2N. The efflux pump KO mutants were more susceptible to these compounds in the presence of efflux inhibitors. We have shown that these four efflux pumps 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                    play a vital role in mediating efflux of different chemical scaffolds. Inhibitors of one or several of these efflux pumps could have a significant impact in the treatment of tuberculosis. The identification and characterization of\n                    <jats:italic>Rv0849<\/jats:italic>\n                    , a new efflux pump belonging to the MFS (major facilitator superfamily) class, are reported.\n                  <\/jats:p>","DOI":"10.1128\/aac.06003-11","type":"journal-article","created":{"date-parts":[[2012,2,7]],"date-time":"2012-02-07T00:51:54Z","timestamp":1328575914000},"page":"2643-2651","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":158,"title":["Efflux Pumps of Mycobacterium tuberculosis Play a Significant Role in Antituberculosis Activity of Potential Drug Candidates"],"prefix":"10.1128","volume":"56","author":[{"given":"Meenakshi","family":"Balganesh","sequence":"first","affiliation":[{"name":"AstraZeneca India Private Limited, Hebbal, Bangalore, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neela","family":"Dinesh","sequence":"additional","affiliation":[{"name":"AstraZeneca India Private Limited, Hebbal, Bangalore, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreevalli","family":"Sharma","sequence":"additional","affiliation":[{"name":"AstraZeneca India Private Limited, Hebbal, Bangalore, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjana","family":"Kuruppath","sequence":"additional","affiliation":[{"name":"AstraZeneca India Private Limited, Hebbal, Bangalore, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju V.","family":"Nair","sequence":"additional","affiliation":[{"name":"AstraZeneca India Private Limited, Hebbal, Bangalore, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umender","family":"Sharma","sequence":"additional","affiliation":[{"name":"AstraZeneca India Private Limited, Hebbal, Bangalore, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cell.2011.02.022","article-title":"Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism","volume":"145","author":"Adams KN","year":"2011","unstructured":"AdamsKN. 2011. 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