{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:56:25Z","timestamp":1791341785049,"version":"4.3.1"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"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":[[2012,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Transcriptional regulators, such as SoxS, RamA, MarA, and Rob, which upregulate the AcrAB efflux pump, have been shown to be associated with multidrug resistance in clinically relevant Gram-negative bacteria. In addition to the multidrug resistance phenotype, these regulators have also been shown to play a role in the cellular metabolism and possibly the virulence potential of microbial cells. As such, the increased expression of these proteins is likely to cause pleiotropic phenotypes.\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Klebsiella pneumoniae<\/jats:named-content>\n                    is a major nosocomial pathogen which can express the SoxS, MarA, Rob, and RamA proteins, and the accompanying paper shows that the increased transcription of\n                    <jats:italic>ramA<\/jats:italic>\n                    is associated with tigecycline resistance (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1128\/AAC.06224-11\">M. Veleba and T. Schneiders<\/jats:ext-link>\n                    , Antimicrob. Agents Chemother. 56:4466\u20134467, 2012). Bioinformatic analyses of the available\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Klebsiella<\/jats:named-content>\n                    genome sequences show that an additional AraC-type regulator is encoded chromosomally. In this work, we characterize this novel AraC-type regulator, hereby called RarA (Regulator of antibiotic resistance A), which is encoded in\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">K. pneumoniae<\/jats:named-content>\n                    ,\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterobacter<\/jats:named-content>\n                    sp. 638,\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Serratia proteamaculans<\/jats:named-content>\n                    568, and\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterobacter cloacae<\/jats:named-content>\n                    . We show that the overexpression of\n                    <jats:italic>rarA<\/jats:italic>\n                    results in a multidrug resistance phenotype which requires a functional AcrAB efflux pump but is independent of the other AraC regulators. Quantitative real-time PCR experiments show that\n                    <jats:italic>rarA<\/jats:italic>\n                    (MGH 78578 KPN_02968) and its neighboring efflux pump operon\n                    <jats:italic>oqxAB<\/jats:italic>\n                    (KPN_02969_02970) are consistently upregulated in clinical isolates collected from various geographical locations (Chile, Turkey, and Germany). Our results suggest that\n                    <jats:italic>rarA<\/jats:italic>\n                    overexpression upregulates the\n                    <jats:italic>oqxAB<\/jats:italic>\n                    efflux pump. Additionally, it appears that\n                    <jats:italic>oqxR<\/jats:italic>\n                    , encoding a GntR-type regulator adjacent to the\n                    <jats:italic>oqxAB<\/jats:italic>\n                    operon, is able to downregulate the expression of the\n                    <jats:italic>oqxAB<\/jats:italic>\n                    efflux pump, where OqxR complementation resulted in reductions to olaquindox MICs.\n                  <\/jats:p>","DOI":"10.1128\/aac.00456-12","type":"journal-article","created":{"date-parts":[[2012,5,29]],"date-time":"2012-05-29T23:24:37Z","timestamp":1338333877000},"page":"4450-4458","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":110,"title":["Characterization of RarA, a Novel AraC Family Multidrug Resistance Regulator in Klebsiella pneumoniae"],"prefix":"10.1128","volume":"56","author":[{"given":"Mark","family":"Veleba","sequence":"first","affiliation":[{"name":"Centre for Infection and Immunity, Queen's University Belfast, Medical Biology Centre, Belfast, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul G.","family":"Higgins","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Agentes Antibacterianos, Departamento de Microbiolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad de Concepci\u00f3n, Concepci\u00f3n, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Seifert","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, 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