{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:13:24Z","timestamp":1791422004194,"version":"4.3.3"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2008,10,1]],"date-time":"2008-10-01T00:00:00Z","timestamp":1222819200000},"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":[[2008,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Salmonella enterica<\/jats:italic>\n            serovar Typhimurium SL1344, in which efflux pump genes (\n            <jats:italic>acrB<\/jats:italic>\n            ,\n            <jats:italic>acrD<\/jats:italic>\n            ,\n            <jats:italic>acrF<\/jats:italic>\n            ,\n            <jats:italic>tolC<\/jats:italic>\n            ) or regulatory genes thereof (\n            <jats:italic>marA<\/jats:italic>\n            ,\n            <jats:italic>soxS<\/jats:italic>\n            ,\n            <jats:italic>ramA<\/jats:italic>\n            ) were inactivated, was grown in the presence of 240 antimicrobial and nonantimicrobial agents in the Biolog Phenotype MicroArray. Mutants lacking\n            <jats:italic>tolC<\/jats:italic>\n            ,\n            <jats:italic>acrB<\/jats:italic>\n            , and\n            <jats:italic>ramA<\/jats:italic>\n            grew significantly worse than other mutants in the presence of 48 agents (some of which have not previously been identified as substrates of AcrAB-TolC) and particularly poorly in the presence of phenothiazines, which are human antipsychotics. MIC testing revealed that the phenothiazine chlorpromazine had antimicrobial activity and synergized with common antibiotics against different\n            <jats:italic>Salmonella<\/jats:italic>\n            serovars and SL1344. Chlorpromazine increased the intracellular accumulation of ethidium bromide, which was ablated in mutants lacking\n            <jats:italic>acrB<\/jats:italic>\n            , suggesting an interaction with AcrB. High-level but not low-level overexpression of\n            <jats:italic>ramA<\/jats:italic>\n            increased the expression of\n            <jats:italic>acrB<\/jats:italic>\n            ; conferred resistance to chloramphenicol, tetracycline, nalidixic acid, and triclosan and organic solvent tolerance; and increased the amount of ethidium bromide accumulated. Chlorpromazine induced the modest overproduction of\n            <jats:italic>ramA<\/jats:italic>\n            but repressed\n            <jats:italic>acrB<\/jats:italic>\n            . These data suggest that phenothiazines are not efflux pump inhibitors but influence gene expression, including that of\n            <jats:italic>acrB<\/jats:italic>\n            , which confers the synergy with antimicrobials observed.\n          <\/jats:p>","DOI":"10.1128\/aac.00661-08","type":"journal-article","created":{"date-parts":[[2008,8,12]],"date-time":"2008-08-12T00:34:37Z","timestamp":1218501277000},"page":"3604-3611","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":123,"title":["RamA Confers Multidrug Resistance in\n            <i>Salmonella enterica<\/i>\n            via Increased Expression of\n            <i>acrB<\/i>\n            , Which Is Inhibited by Chlorpromazine"],"prefix":"10.1128","volume":"52","author":[{"given":"Andrew M.","family":"Bailey","sequence":"first","affiliation":[{"name":"Antimicrobial Agents Research Group, Department of Immunity and Infection, The Medical School, The University of Birmingham, Birmingham B15 2TT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian T.","family":"Paulsen","sequence":"additional","affiliation":[{"name":"The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, Maryland 20850"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J. V.","family":"Piddock","sequence":"additional","affiliation":[{"name":"Antimicrobial Agents Research Group, Department of Immunity and Infection, The Medical School, The University of Birmingham, Birmingham B15 2TT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00084-08"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.5.1185-1193.1998"},{"key":"e_1_3_2_4_2","first-page":"725","volume":"18","year":"2004","unstructured":"Amaral, L., M. Viveiros, and J. Molnar. 2004. Antimicrobial activity of phenothiazines. 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