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

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 -lactams but not imipenem. In this study, enhanced efflux-mediated fluoroquinolone resistance...

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Main Authors: Yuji eMorita, Junko eTomida, Yoshiaki eKawamura
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-01-01
Series:Frontiers in Microbiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00008/full
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author Yuji eMorita
Junko eTomida
Yoshiaki eKawamura
author_facet Yuji eMorita
Junko eTomida
Yoshiaki eKawamura
author_sort Yuji eMorita
collection DOAJ
description 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 -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.
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spelling doaj.art-d9781a951610496d9ac78798d421c3082022-12-22T03:34:20ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2015-01-01610.3389/fmicb.2015.00008124046Efflux-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 operonYuji eMorita0Junko eTomida1Yoshiaki eKawamura2Aichi Gakuin UniversityAichi Gakuin UniversityAichi Gakuin UniversityThe 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 -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.http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00008/fullPseudomonas aeruginosaeffluxmexXY-oprAmexEF-oprNmexS
spellingShingle Yuji eMorita
Junko eTomida
Yoshiaki eKawamura
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
Frontiers in Microbiology
Pseudomonas aeruginosa
efflux
mexXY-oprA
mexEF-oprN
mexS
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Pseudomonas aeruginosa
efflux
mexXY-oprA
mexEF-oprN
mexS
url http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00008/full
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AT junkoetomida effluxmediatedfluoroquinoloneresistanceinthemultidrugresistantpseudomonasaeruginosaclinicalisolatepa7identificationofanovelmexsvariantinvolvedinupregulationofthemexefoprnmultidrugeffluxoperon
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