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Also, RND pumps have been implicated in physiological processes, with roles in the virulence mechanisms of several pathogenic bacteria. We have previously shown that the BepC outer membrane factor of\n                    <jats:italic>Brucella suis<\/jats:italic>\n                    is involved in the efflux of diverse drugs, probably as part of a tripartite complex with an inner membrane translocase. In the present work, we characterize two membrane fusion protein-RND translocases of\n                    <jats:italic>B. suis<\/jats:italic>\n                    encoded by the\n                    <jats:italic>bepDE<\/jats:italic>\n                    and\n                    <jats:italic>bepFG<\/jats:italic>\n                    loci. MIC assays showed that the\n                    <jats:italic>B. suis<\/jats:italic>\n                    \u0394\n                    <jats:italic>bepE<\/jats:italic>\n                    mutant was more sensitive to deoxycholate (DOC), ethidium bromide, and crystal violet. Furthermore, multicopy\n                    <jats:italic>bepDE<\/jats:italic>\n                    increased resistance to DOC and crystal violet and also to other drugs, including ampicillin, norfloxacin, ciprofloxacin, tetracycline, and doxycycline. In contrast to the \u0394\n                    <jats:italic>bepE<\/jats:italic>\n                    mutant, the resistance profile of\n                    <jats:italic>B. suis<\/jats:italic>\n                    remained unaltered when the other RND gene (\n                    <jats:italic>bepG<\/jats:italic>\n                    ) was deleted. However, the \u0394\n                    <jats:italic>bepE<\/jats:italic>\n                    \u0394\n                    <jats:italic>bepG<\/jats:italic>\n                    double mutant showed a more severe phenotype than the \u0394\n                    <jats:italic>bepE<\/jats:italic>\n                    mutant, indicating that BepFG also contributes to drug resistance. An open reading frame (\n                    <jats:italic>bepR<\/jats:italic>\n                    ) coding for a putative regulatory protein of the TetR family was found upstream of the\n                    <jats:italic>bepDE<\/jats:italic>\n                    locus. BepR strongly repressed the activity of the\n                    <jats:italic>bepDE<\/jats:italic>\n                    promoter, but DOC released the repression mediated by BepR. A clear induction of the\n                    <jats:italic>bepFG<\/jats:italic>\n                    promoter activity was observed only in the BepDE-defective mutant, indicating a regulatory interplay between the two RND efflux pumps. Although only the BepFG-defective mutant showed a moderate attenuation in model cells, the activities of both\n                    <jats:italic>bepDE<\/jats:italic>\n                    and\n                    <jats:italic>bepFG<\/jats:italic>\n                    promoters were induced in the intracellular environment of HeLa cells. Our results show that\n                    <jats:italic>B. suis<\/jats:italic>\n                    harbors two functional RND efflux pumps that may contribute to virulence.\n                  <\/jats:p>","DOI":"10.1128\/jb.01198-08","type":"journal-article","created":{"date-parts":[[2009,2,7]],"date-time":"2009-02-07T04:01:19Z","timestamp":1233979279000},"page":"2530-2540","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Interplay between Two RND Systems Mediating Antimicrobial Resistance in\n                    <i>Brucella suis<\/i>"],"prefix":"10.1128","volume":"191","author":[{"given":"Fernando A.","family":"Martin","sequence":"first","affiliation":[{"name":"Fundacio\u0301n Instituto Leloir, IIBBA CONICET and FCEyN, Universidad de Buenos Aires, Patricias Argentinas 435, (C1405BWE) Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana M.","family":"Posadas","sequence":"additional","affiliation":[{"name":"Fundacio\u0301n Instituto Leloir, IIBBA CONICET and FCEyN, Universidad de Buenos Aires, Patricias Argentinas 435, (C1405BWE) Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela C.","family":"Carrica","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnologi\u0301a, CICVyA, INTA-Castelar, Las Caban\u0303as y Los Reseros s\/n (B1712WAA) Castelar, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvio L.","family":"Cravero","sequence":"additional","affiliation":[{"name":"Instituto de Biotecnologi\u0301a, CICVyA, INTA-Castelar, Las Caban\u0303as y Los Reseros s\/n (B1712WAA) Castelar, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"O'Callaghan","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, ESPRI 26, Universite\u0301 de Montpellier 1, ERA4204, UFR de Me\u0301decine, CS 83021, Avenue Kennedy, 30908 NIMES Cedex 02, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeles","family":"Zorreguieta","sequence":"additional","affiliation":[{"name":"Fundacio\u0301n Instituto Leloir, IIBBA CONICET and FCEyN, Universidad de Buenos Aires, Patricias Argentinas 435, (C1405BWE) Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.6.1923-1929.2005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400164200"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s10254-003-0008-y","volume":"147","year":"2003","unstructured":"Andersen, C. 2003. 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