title: Mutations in PA2491 (mexS) promote MexT-dependent mexEF-oprN expression and multidrug resistance in a clinical strain of Pseudomonas aeruginosa.
abstract: Disruption of the PA2491 gene in a mini-Tn5-tet insertion mutant of a clinical isolate of Pseudomonas aeruginosa increased expression of the mexEF-oprN multidrug efflux genes and decreased production of outer membrane protein OprD, concomitant with enhanced resistance to chloramphenicol, quinolones, and imipenem, which was reminiscent of previously described nfxC mutants. PA2491 encodes a probable oxidoreductase previously shown to be positively regulated by the MexT positive regulator of mexEF-oprN expression (T. Kohler, S. F. Epp, L. K. Curty, and J. C. Pechere, J. Bacteriol. 181:6300-6305, 1999). Spontaneous multidrug-resistant mutants of the P. aeruginosa clinical isolate hyperexpressing mexEF-oprN and showing reduced production of OprD were readily selected in vitro, and all of them were shown to carry mutations in PA2491, highlighting the probable significance of such mutations as determinants of MexEF-OprN-mediated multidrug resistance in vivo.
authors.affiliation: Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Mara L
authors.initials: ML
authors.lastname: Sobel
authors.forename: Shadi
authors.initials: S
authors.lastname: Neshat
authors.forename: Keith
authors.initials: K
authors.lastname: Poole
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001693:Biological Transport, Active; D002701:Chloramphenicol / Q000494:pharmacology; D004251:DNA Transposable Elements; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D015378:Imipenem / Q000494:pharmacology; D016254:Mutagenesis, Insertional; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D018272:Porins / Q000032:analysis; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; C105708:OprN protein, Pseudomonas aeruginosa; D018272:Porins; D015363:Quinolones; C077157:OprD protein, Pseudomonas aeruginosa; D002701:Chloramphenicol; D015378:Imipenem; D010088:Oxidoreductases