title: RamA is an alternate activator of the multidrug resistance cascade in Enterobacter aerogenes.
abstract: 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 beta-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.
authors.affiliation: Enveloppe Bactérienne, Perméabilité et Antibiotiques, EA 2197, IFR 48, Facultés de Médecine et Pharmacie, Université de la Méditerranée, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Chollet
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Chevalier
authors.forename: Claude
authors.initials: C
authors.lastname: Bollet
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Pages
authors.forename: Anne
authors.initials: A
authors.lastname: Davin-Regli
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D002701:Chloramphenicol / Q000378:metabolism; D003470:Culture Media; D004269:DNA, Bacterial / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D021902:Enterobacter aerogenes / Q000187:drug effects / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D019450:Genes, MDR / Q000235:genetics*; D015151:Immunoblotting; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009876:Operon / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D018272:Porins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics*; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D001425:Bacterial Outer Membrane Proteins; D003470:Culture Media; D004269:DNA, Bacterial; D018272:Porins; C489154:RamA protein, Enterobacter aerogenes; D014157:Transcription Factors; D002701:Chloramphenicol; D001616:beta-Galactosidase