{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:56:22Z","timestamp":1790772982455,"version":"4.1.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"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":[[2013,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            RarA is an AraC-type regulator in\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            , which, when overexpressed, confers a low-level multidrug-resistant (MDR) phenotype linked to the upregulation of both the\n            <jats:italic>acrAB<\/jats:italic>\n            and\n            <jats:italic>oqxAB<\/jats:italic>\n            efflux genes. Increased\n            <jats:italic>rarA<\/jats:italic>\n            expression has also been shown to be integral in the development of tigecycline resistance in the absence of\n            <jats:italic>ramA<\/jats:italic>\n            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            . Given its phenotypic role in MDR, microarray analyses were performed to determine the RarA regulon. Transcriptome analysis was undertaken using strains Ecl8\u0394\n            <jats:italic>rarA<\/jats:italic>\n            \/pACrarA-2 (\n            <jats:italic>rarA<\/jats:italic>\n            -expressing construct) and Ecl8\u0394\n            <jats:italic>rarA<\/jats:italic>\n            \/pACYC184 (vector-only control) using bespoke microarray slides consisting of probes derived from the genomic sequences of\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            MGH 78578 (NC_009648.1) and Kp342 (NC_011283.1). Our results show that\n            <jats:italic>rarA<\/jats:italic>\n            overexpression resulted in the differential expression of 66 genes (42 upregulated and 24 downregulated). Under the COG (clusters of orthologous groups) functional classification, the majority of affected genes belonged to the category of cell envelope biogenesis and posttranslational modification, along with genes encoding the previously uncharacterized transport proteins (e.g., KPN_03141,\n            <jats:italic>sdaCB<\/jats:italic>\n            , and\n            <jats:italic>leuE<\/jats:italic>\n            ) and the porin OmpF. However, genes associated with energy production and conversion and amino acid transport\/metabolism (e.g.,\n            <jats:italic>nuoA<\/jats:italic>\n            ,\n            <jats:italic>narJ<\/jats:italic>\n            , and\n            <jats:italic>proWX<\/jats:italic>\n            ) were found to be downregulated. Biolog phenotype analyses demonstrated that\n            <jats:italic>rarA<\/jats:italic>\n            overexpression confers enhanced growth of the overexpresser in the presence of several antibiotic classes (i.e., beta-lactams and fluoroquinolones), the antifungal\/antiprotozoal compound clioquinol, disinfectants (8-hydroxyquinoline), protein synthesis inhibitors (i.e., minocycline and puromycin), membrane biogenesis agents (polymyxin B and amitriptyline), DNA synthesis (furaltadone), and the cytokinesis inhibitor (sanguinarine). Both our transcriptome and phenotypic microarray data support and extend the role of RarA in the MDR phenotype of\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:p>","DOI":"10.1128\/aac.01998-12","type":"journal-article","created":{"date-parts":[[2013,1,15]],"date-time":"2013-01-15T04:53:42Z","timestamp":1358225622000},"page":"1603-1609","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":52,"title":["Elucidating the Regulon of Multidrug Resistance Regulator RarA in Klebsiella pneumoniae"],"prefix":"10.1128","volume":"57","author":[{"given":"Shyamasree","family":"De Majumdar","sequence":"first","affiliation":[{"name":"Centre for Infection and Immunity, Queen's University Belfast, Belfast, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Veleba","sequence":"additional","affiliation":[{"name":"Centre for Infection and Immunity, Queen's University Belfast, Belfast, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Finn","sequence":"additional","affiliation":[{"name":"UCD Centre for Molecular Innovation and Drug Design, School of Public Health, Physiotherapy &amp; Population Science, University College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9amus","family":"Fanning","sequence":"additional","affiliation":[{"name":"UCD Centre for Molecular Innovation and Drug Design, School of Public Health, Physiotherapy &amp; Population Science, University College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thamarai","family":"Schneiders","sequence":"additional","affiliation":[{"name":"Centre for Infection 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