{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:49:51Z","timestamp":1791236991402,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","funder":[{"name":"NIH","award":["T32 AI55396"],"award-info":[{"award-number":["T32 AI55396"]}]},{"name":"NIH","award":["T32 AI007044"],"award-info":[{"award-number":["T32 AI007044"]}]},{"name":"the recipient of the Merle A. Sande-Pfizer Fellowship in International Infectious Diseases","award":["AI036396 and AI057141"],"award-info":[{"award-number":["AI036396 and AI057141"]}]},{"name":"NIH Director's Pioneer Award","award":["OD006782"],"award-info":[{"award-number":["OD006782"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,8,1]]},"DOI":"10.1093\/infdis\/jiu095","type":"journal-article","created":{"date-parts":[[2014,2,15]],"date-time":"2014-02-15T04:45:11Z","timestamp":1392439511000},"page":"456-466","source":"Crossref","is-referenced-by-count":127,"title":["Verapamil, and Its Metabolite Norverapamil, Inhibit Macrophage-induced, Bacterial Efflux Pump-mediated Tolerance to Multiple Anti-tubercular Drugs"],"prefix":"10.1093","volume":"210","author":[{"given":"Kristin N.","family":"Adams","sequence":"first","affiliation":[{"name":"Department of Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Szumowski","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalita","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"Department of Microbiology"},{"name":"Department of Medicine, Division of Infectious Diseases"},{"name":"Department of Immunology, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,2,14]]},"reference":[{"key":"key\n\t\t\t\t20180328144331_JIU095C1","first-page":"1079","article-title":"Controlled clinical trial of short-course (6-month) regimens of chemotherapy for treatment of pulmonary tuberculosis","volume":"1","year":"1972","journal-title":"Lancet"},{"key":"key\n\t\t\t\t20180328144331_JIU095C2","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1164\/rccm.200904-0536OC","article-title":"Shortening treatment in adults with noncavitary tuberculosis and 2-month culture conversion","volume":"180","author":"Johnson","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"key\n\t\t\t\t20180328144331_JIU095C3","doi-asserted-by":"crossref","first-page":"e120","DOI":"10.1371\/journal.pmed.0040120","article-title":"Why is long-term therapy required to cure tuberculosis?","volume":"4","author":"Connolly","year":"2007","journal-title":"PLoS Med"},{"key":"key\n\t\t\t\t20180328144331_JIU095C4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.tube.2003.08.003","article-title":"M. tuberculosis persistence, latency, and drug tolerance","volume":"84","author":"Gomez","year":"2004","journal-title":"Tuberculosis"},{"key":"key\n\t\t\t\t20180328144331_JIU095C5","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nrmicro2236","article-title":"The spectrum of latent tuberculosis: rethinking the biology and intervention strategies","volume":"7","author":"Barry","year":"2009","journal-title":"Nat Rev Microbiol"},{"key":"key\n\t\t\t\t20180328144331_JIU095C6","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/35016103","article-title":"A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis","volume":"405","author":"Stover","year":"2000","journal-title":"Nature"},{"key":"key\n\t\t\t\t20180328144331_JIU095C7","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1126\/science.1106753","article-title":"A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis","volume":"307","author":"Andries","year":"2005","journal-title":"Science"},{"key":"key\n\t\t\t\t20180328144331_JIU095C8","doi-asserted-by":"crossref","first-page":"25273","DOI":"10.1074\/jbc.M803899200","article-title":"Diarylquinolines are bactericidal for dormant mycobacteria as a result of disturbed ATP homeostasis","volume":"283","author":"Koul","year":"2008","journal-title":"J Biol Chem"},{"key":"key\n\t\t\t\t20180328144331_JIU095C9","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1056\/NEJMoa0808427","article-title":"The diarylquinoline TMC207 for multidrug-resistant tuberculosis","volume":"360","author":"Diacon","year":"2009","journal-title":"N Engl J Med"},{"key":"key\n\t\t\t\t20180328144331_JIU095C10","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1164\/rccm.200807-1152OC","article-title":"Sterilizing activity of R207910 (TMC207)-containing regimens in the murine model of tuberculosis","volume":"180","author":"Ibrahim","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"key\n\t\t\t\t20180328144331_JIU095C11","doi-asserted-by":"crossref","first-page":"39","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","year":"2011","journal-title":"Cell"},{"key":"key\n\t\t\t\t20180328144331_JIU095C12","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.2165\/11317030-000000000-00000","article-title":"Efflux-mediated drug resistance in bacteria: an update","volume":"69","author":"Li","year":"2009","journal-title":"Drugs"},{"key":"key\n\t\t\t\t20180328144331_JIU095C13","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1164\/rccm.201011-1924OC","article-title":"Rifampicin reduces susceptibility to ofloxacin in rifampicin-resistant Mycobacterium tuberculosis through efflux","volume":"184","author":"Louw","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"key\n\t\t\t\t20180328144331_JIU095C14","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1164\/rccm.201304-0650OC","article-title":"Acceleration of tuberculosis treatment by adjunctive therapy with verapamil as an efflux inhibitor","volume":"188","author":"Gupta","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"key\n\t\t\t\t20180328144331_JIU095C15","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1128\/JCM.33.9.2324-2327.1995","article-title":"Colorimetric method for determining MICs of antimicrobial agents for Mycobacterium tuberculosis","volume":"33","author":"Yajko","year":"1995","journal-title":"J Clin Microbiol"},{"key":"key\n\t\t\t\t20180328144331_JIU095C16","volume-title":"Handbook of anti-Tuberculosis agents","author":"Anonymous","year":"2008"},{"key":"key\n\t\t\t\t20180328144331_JIU095C17","doi-asserted-by":"crossref","first-page":"5167","DOI":"10.1128\/AAC.00610-10","article-title":"Rv1218c, an ABC transporter of Mycobacterium tuberculosis with implications in drug discovery","volume":"54","author":"Balganesh","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"key\n\t\t\t\t20180328144331_JIU095C18","doi-asserted-by":"crossref","first-page":"e10069","DOI":"10.1371\/journal.pone.0010069","article-title":"A Mycobacterium tuberculosis sigma factor network responds to cell-envelope damage by the promising anti-mycobacterial thioridazine","volume":"5","author":"Dutta","year":"2010","journal-title":"PLoS One"},{"key":"key\n\t\t\t\t20180328144331_JIU095C19","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1093\/jac\/dkq186","article-title":"Piperine as an inhibitor of Rv1258c, a putative multidrug efflux pump of Mycobacterium tuberculosis","volume":"65","author":"Sharma","year":"2010","journal-title":"J Antimicrob Chemother"},{"key":"key\n\t\t\t\t20180328144331_JIU095C20","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1093\/infdis\/165.2.322","article-title":"J774 macrophages secrete antibiotics via organic anion transporters","volume":"165","author":"Cao","year":"1992","journal-title":"J Infect Dis"},{"key":"key\n\t\t\t\t20180328144331_JIU095C21","first-page":"223","article-title":"Influence of piperine on rifampicin blood levels in patients of pulmonary tuberculosis","volume":"33","author":"Zutshi","year":"1985","journal-title":"J Assoc of Physicians India"},{"key":"key\n\t\t\t\t20180328144331_JIU095C22","doi-asserted-by":"crossref","first-page":"8327","DOI":"10.1073\/pnas.0503272102","article-title":"Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages","volume":"102","author":"Rengarajan","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"key\n\t\t\t\t20180328144331_JIU095C23","first-page":"81","article-title":"Antimicrobial efflux pumps and Mycobacterium tuberculosis drug tolerance: evolutionary considerations","volume":"374","author":"Szumowski","year":"2013","journal-title":"Curr Top Microbiol Immunol"},{"key":"key\n\t\t\t\t20180328144331_JIU095C24","first-page":"69","article-title":"Inhibitors of Ca2+ and K+ transport enhance intracellular killing of M. tuberculosis by non-killing macrophages","volume-title":"In Vivo","author":"Martins","year":"2008"},{"key":"key\n\t\t\t\t20180328144331_JIU095C25","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1128\/AAC.47.3.917-922.2003","article-title":"Clinical concentrations of thioridazine kill intracellular multidrug-resistant Mycobacterium tuberculosis","volume":"47","author":"Ordway","year":"2003","journal-title":"Antimicrob Agents Chemother"},{"key":"key\n\t\t\t\t20180328144331_JIU095C26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2165\/00003495-198938010-00003","article-title":"Verapamil: an updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension","volume":"38","author":"McTavish","year":"1989","journal-title":"Drugs"},{"key":"key\n\t\t\t\t20180328144331_JIU095C27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1526-4610.2008.01298.x","article-title":"Verapamil for cluster headache: clinical pharmacology and possible mode of action","volume":"49","author":"Tfelt-Hansen","year":"2009","journal-title":"Headache"},{"key":"key\n\t\t\t\t20180328144331_JIU095C28","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1159\/000138185","article-title":"Steady state verapamil tissue distribution in the dog: differing tissue accumulation","volume":"32","author":"Schwartz","year":"1986","journal-title":"Pharmacology"},{"key":"key\n\t\t\t\t20180328144331_JIU095C29","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1080\/004982500237857","article-title":"Comparison of the pharmacokinetics of verapamil in the pregnant and non-pregnant rabbit: study of maternal and foetal tissue levels","volume":"30","author":"Solans","year":"2000","journal-title":"Xenobiotica"},{"key":"key\n\t\t\t\t20180328144331_JIU095C30","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1080\/10408390601062054","article-title":"Black pepper and its pungent principle-piperine: a review of diverse physiological effects","volume":"47","author":"Srinivasan","year":"2007","journal-title":"Crit Rev Food Sci Nutr"},{"key":"key\n\t\t\t\t20180328144331_JIU095C31","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.ijantimicag.2009.12.019","article-title":"Thioridazine cures extensively drug-resistant tuberculosis (XDR-TB) and the need for global trials is now!","volume":"35","author":"Amaral","year":"2010","journal-title":"Int J Antimicrob Agents"},{"key":"key\n\t\t\t\t20180328144331_JIU095C32","first-page":"748","article-title":"Activation of pyrazinamide and nicotinamide in acidic environments in vitro","volume":"70","author":"McDermott","year":"1954","journal-title":"Am Rev Tuberc"},{"key":"key\n\t\t\t\t20180328144331_JIU095C33","article-title":"Treatment of Tuberculosis Guidelines, 4th ed","year":"2010"},{"key":"key\n\t\t\t\t20180328144331_JIU095C34","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1128\/AAC.01570-07","article-title":"Identification of mutations related to streptomycin resistance in clinical isolates of Mycobacterium tuberculosis and possible involvement of efflux mechanism","volume":"52","author":"Spies","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"key":"key\n\t\t\t\t20180328144331_JIU095C35","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.1128\/AAC.01577-08","article-title":"A balancing act: efflux\/influx in mycobacterial drug resistance","volume":"53","author":"Louw","year":"2009","journal-title":"Antimicrob Agents Chemother"},{"key":"key\n\t\t\t\t20180328144331_JIU095C36","doi-asserted-by":"crossref","first-page":"e34538","DOI":"10.1371\/journal.pone.0034538","article-title":"Contribution of efflux to the emergence of isoniazid and multidrug resistance in Mycobacterium tuberculosis","volume":"7","author":"Machado","year":"2012","journal-title":"PLoS One"},{"key":"key\n\t\t\t\t20180328144331_JIU095C37","first-page":"535","article-title":"Effect of efflux pump inhibitors on drug susceptibility of ofloxacin resistant Mycobacterium tuberculosis isolates","volume":"133","author":"Singh","year":"2011","journal-title":"Indian J Med Res"},{"key":"key\n\t\t\t\t20180328144331_JIU095C38","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1128\/AAC.01462-13","article-title":"Efflux inhibition with verapamil potentiates bedaquiline in Mycobacterium tuberculosis","volume":"58","author":"Gupta","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"key":"key\n\t\t\t\t20180328144331_JIU095C39","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1054\/tuld.1998.0002","article-title":"Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update","volume":"79","author":"Ramaswamy","year":"1998","journal-title":"Tuber Lung Dis"},{"key":"key\n\t\t\t\t20180328144331_JIU095C40","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.tube.2010.07.004","article-title":"Bactericidal activity of the diarylquinoline TMC207 against Mycobacterium tuberculosis outside and within cells","volume":"90","author":"Dhillon","year":"2010","journal-title":"Tuberculosis"},{"key":"key\n\t\t\t\t20180328144331_JIU095C41","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/0006-2952(95)00174-X","article-title":"Reversal of multidrug resistance by verapamil analogues","volume":"50","author":"Pereira","year":"1995","journal-title":"Biochem Pharmacol"},{"key":"key\n\t\t\t\t20180328144331_JIU095C42","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1093\/cvr\/12.4.247","article-title":"Comparative cardiovascular actions of verapamil and its major metabolites in the anaesthetised dog","volume":"12","author":"Neugebauer","year":"1978","journal-title":"Cardiovasc Res"},{"key":"key\n\t\t\t\t20180328144331_JIU095C43","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s00228-006-0154-7","article-title":"Cardiovascular effects of (R)- and (S)-verapamil and racemic verapamil in humans: a placebo-controlled study","volume":"62","author":"Busse","year":"2006","journal-title":"Eur J Clin Pharmacol"},{"key":"key\n\t\t\t\t20180328144331_JIU095C44","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1164\/rccm.200603-360OC","article-title":"Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis","volume":"174","author":"Burman","year":"2006","journal-title":"Am J Respir Crit Care Med"},{"key":"key\n\t\t\t\t20180328144331_JIU095C45","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1164\/rccm.200901-0078OC","article-title":"Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis","volume":"180","author":"Dorman","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"key\n\t\t\t\t20180328144331_JIU095C46","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S0090-9556(24)15345-7","article-title":"Verapamil metabolite exposure in older and younger men during steady-state oral verapamil administration","volume":"28","author":"Abernethy","year":"2000","journal-title":"Drug Metab Dispos"},{"key":"key\n\t\t\t\t20180328144331_JIU095C47","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0002-8703(92)90951-Q","article-title":"Low-dose calcium pretreatment to prevent verapamil-induced hypotension","volume":"124","author":"Kuhn","year":"1992","journal-title":"Am Heart J"},{"key":"key\n\t\t\t\t20180328144331_JIU095C48","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1378\/chest.94.5.954","article-title":"Near-total reduction in verapamil bioavailability by rifampin: electrocardiographic correlates","volume":"94","author":"Barbarash","year":"1988","journal-title":"Chest"},{"key":"key\n\t\t\t\t20180328144331_JIU095C49","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s15010-004-3097-x","article-title":"Mycobacterium tuberculosis isolate with a distinct genomic identity overexpresses a tap-like efflux pump","volume":"32","author":"Siddiqi","year":"2004","journal-title":"Infection"},{"key":"key\n\t\t\t\t20180328144331_JIU095C50","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1128\/AAC.9.3.393","article-title":"Inhibition of dihydrostreptomycin binding to Mycobacterium smegmatis by monovalent and divalent cation salts","volume":"9","author":"Beggs","year":"1976","journal-title":"Antimicrob Agents Chemother"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/210\/3\/456\/13804954\/jiu095.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T21:25:05Z","timestamp":1746134705000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/210\/3\/456\/2908518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,14]]},"references-count":50,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2014,2,14]]},"published-print":{"date-parts":[[2014,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiu095","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,14]]}}}