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Antimicrobial Agents and Chemotherapy, July 2004, p. 2518-2523, Vol. 48, No. 7
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.7.2518-2523.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

RamA Is an Alternate Activator of the Multidrug Resistance Cascade in Enterobacter aerogenes

Enveloppe Bactérienne, Perméabilité et Antibiotiques, EA 2197, IFR 48, Facultés de Médecine et Pharmacie, Université de la Méditerranée, 13385 Marseille Cedex 05, France

Received 4 November 2003/ Returned for modification 29 January 2004/ Accepted 17 March 2004

Multidrug resistance (MDR) in Enterobacter aerogenes can be mediated by induction of MarA, which is triggered by certain antibiotics and phenolic compounds. In this study, we identified the gene encoding RamA, a 113-amino-acid regulatory protein belonging to the AraC-XylS transcriptional activator family, in the Enterobacter aerogenes ATCC 13048 type strain and in a clinical multiresistant isolate. Overexpression of RamA induced an MDR phenotype in drug-susceptible Escherichia coli JM109 and E. aerogenes ATCC 13048, as demonstrated by 2- to 16-fold-increased resistance to ß-lactams, tetracycline, chloramphenicol, and quinolones, a decrease in porin production, and increased production of AcrA, a component of the AcrAB-TolC drug efflux pump. We show that RamA enhances the transcription of the marRAB operon but is also able to induce an MDR phenotype in a mar-deleted strain. We demonstrate here that RamA is a transcriptional activator of the Mar regulon and is also a self-governing activator of the MDR cascade.

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