title: Efflux-mediated fluoroquinolone resistance in the multidrug-resistant Pseudomonas aeruginosa clinical isolate PA7: identification of a novel MexS variant involved in upregulation of the mexEF-oprN multidrug efflux operon.
abstract: The emergence of multidrug-resistant Pseudomonas aeruginosa has become a serious problem in medical settings. P. aeruginosa clinical isolate PA7 is resistant to fluoroquinolones, aminoglycosides, and most β-lactams but not imipenem. In this study, enhanced efflux-mediated fluoroquinolone resistance of PA7 was shown to reflect increased expression of two resistance nodulation cell division (RND) -type multidrug efflux operons, mexEF-oprN and mexXY-oprA. Such a clinical isolate has rarely been reported because MexEF-OprN-overproducing mutants often increase susceptibility to aminoglycosides apparently owing to impairment of the MexXY system. A mutant of PA7 lacking three RND-type multidrug efflux operons (mexAB-oprM, mexEF-oprN, and mexXY-oprA) was susceptible to all anti-pseudomonas agents we tested, supporting an idea that these RND-type multidrug efflux transporters are molecular targets to overcome multidrug resistance in P. aeruginosa. mexEF-oprN-upregulation in P. aeruginosa PA7 was shown due to a MexS variant harboring the Valine-155 amino acid residue. This is the first genetic evidence shown that a MexS variant causes mexEF-oprN-upregulation in P. aeruginosa clinical isolates.
authors: Department of Microbiology, School of Pharmacy, Aichi Gakuin University Nagoya, Japan.
authors: Yuji
authors: Y
authors: Morita
authors: Department of Microbiology, School of Pharmacy, Aichi Gakuin University Nagoya, Japan.
authors: Junko
authors: J
authors: Tomida
authors: Department of Microbiology, School of Pharmacy, Aichi Gakuin University Nagoya, Japan.
authors: Yoshiaki
authors: Y
authors: Kawamura
keywords: Pseudomonas aeruginosa; efflux; mexEF-oprN; mexS; mexXY-oprA
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