{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T22:09:22Z","timestamp":1789855762909,"version":"4.0.1"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2016,8,22]],"date-time":"2016-08-22T00:00:00Z","timestamp":1471824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-62690"],"award-info":[{"award-number":["MOP-62690"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["PP00P3_144823"],"award-info":[{"award-number":["PP00P3_144823"]}],"id":[{"id":"10.13039\/501100001711","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":[[2016,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Nosocomial infections with\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterococcus faecalis<\/jats:named-content>\n            are an emerging health problem. However, drug efflux pumps contributing to intrinsic drug resistance are poorly studied in this Gram-positive pathogen. In this study, we functionally investigated seven heterodimeric ABC transporters of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. faecalis<\/jats:named-content>\n            that are annotated as drug efflux pumps. Deletion of\n            <jats:italic>ef0789-ef0790<\/jats:italic>\n            on the chromosome of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. faecalis<\/jats:named-content>\n            resulted in increased susceptibility to daunorubicin, doxorubicin, ethidium, and Hoechst 33342, and the corresponding transporter was named EfrCD. Unexpectedly, the previously described heterodimeric multidrug ABC transporter EfrAB contributes marginally to drug efflux in the endogenous context of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. faecalis<\/jats:named-content>\n            . In contrast, heterologous expression in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Lactococcus lactis<\/jats:named-content>\n            revealed that EfrAB, EfrCD, and the product of\n            <jats:italic>ef2226-ef2227<\/jats:italic>\n            (EfrEF) mediate the efflux of fluorescent substrates and confer resistance to multiple dyes and drugs, including fluoroquinolones. Four of seven transporters failed to exhibit drug efflux activity for the set of drugs and dyes tested, even upon overexpression in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">L. lactis<\/jats:named-content>\n            . Since all seven transporters were purified as heterodimers after overexpression in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">L. lactis<\/jats:named-content>\n            , a lack of drug efflux activity is not attributed to poor expression or protein aggregation. Reconstitution of the purified multidrug transporters EfrAB, EfrCD, and EfrEF in proteoliposomes revealed functional coupling between ATP hydrolysis and drug binding. Our analysis creates an experimental basis for the accurate prediction of drug efflux transporters and indicates that many annotated multidrug efflux pumps might be incapable of drug transport and thus might fulfill other physiological functions in the cell.\n          <\/jats:p>","DOI":"10.1128\/aac.00661-16","type":"journal-article","created":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T02:58:59Z","timestamp":1467773939000},"page":"5400-5411","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":56,"title":["The Heterodimeric ABC Transporter EfrCD Mediates Multidrug Efflux in Enterococcus faecalis"],"prefix":"10.1128","volume":"60","author":[{"given":"Lea M.","family":"H\u00fcrlimann","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Corradi","sequence":"additional","affiliation":[{"name":"Centre for Molecular Simulation and Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hohl","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido V.","family":"Bloemberg","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Peter","family":"Tieleman","sequence":"additional","affiliation":[{"name":"Centre for Molecular Simulation and Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus A.","family":"Seeger","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.026385-0"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2761"},{"key":"e_1_3_3_4_2","volume-title":"Enterococci: from commensals to leading causes of drug resistant infection","author":"Kristich CJ","year":"2014","unstructured":"Kristich CJ, Rice LB, Arias CA. 6 February 2014. Enterococcal infection\u2014treatment and antibiotic resistance. In Gilmore MS, Clewell DB, Ike Y, Shankar N (ed), Enterococci: from commensals to leading causes of drug resistant infection. Massachusetts Eye and Ear Infirmary, Boston, MA. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK190420\/."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2013.01.006"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1080613"},{"key":"e_1_3_3_7_2","first-page":"179","article-title":"Enterococcus faecalis multi-drug resistance transporters: application for antibiotic discovery","volume":"3","author":"Davis DR","year":"2001","unstructured":"Davis DR, McAlpine JB, Pazoles CJ, Talbot MK, Alder EA, White C, Jonas BM, Murray BE, Weinstock GM, Rogers BL. 2001. Enterococcus faecalis multi-drug resistance transporters: application for antibiotic discovery. 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