AUTHOR=Morita Yuji , Tomida Junko , Kawamura Yoshiaki 

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

JOURNAL=Frontiers in Microbiology

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.00008

DOI=10.3389/fmicb.2015.00008

ISSN=1664-302X

ABSTRACT=<p>The emergence of multidrug-resistant <italic>Pseudomonas aeruginosa</italic> has become a serious problem in medical settings. <italic>P. aeruginosa</italic> 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, <italic>mexEF-oprN</italic> and <italic>mexXY-oprA</italic>. 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 (<italic>mexAB-oprM</italic>, <italic>mexEF-oprN</italic>, and <italic>mexXY-oprA)</italic> 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 <italic>P. aeruginosa</italic>. <italic>mexEF-oprN</italic>-upregulation in <italic>P. aeruginosa</italic> 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 <italic>mexEF-oprN</italic>-upregulation in <italic>P. aeruginosa</italic> clinical isolates.</p>