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Mutations in the gyrA, parC, and mexR genes provide functional insights into the fluoroquinolone-resistant Pseudomonas aeruginosa isolated in Vietnam

Authors Nguyen KV, Nguyen TV, Nguyen HTT, Le DV

Received 28 July 2017

Accepted for publication 22 November 2017

Published 28 February 2018 Volume 2018:11 Pages 275—282


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Joachim Wink

Kinh Van Nguyen,1,2,* Trung Vu Nguyen,1,3,* Hang Thi Thuy Nguyen,4 Duyet Van Le1

1Clinical Laboratories, National Hospital for Tropical Diseases, 2Infectious Department, Hanoi Medical University, 3Microbiology Department, Hanoi Medical University, 4Department of Microbiology, National Geriatric Hospital, Hanoi, Vietnam

*These authors contributed equally to this work

Introduction: Pseudomonas aeruginosa has many mechanisms of resistance to fluoroquinolones. The main mechanism is to change the effect of two enzymes that open the DNA helix – the enzyme DNA gyrase (gyrA) and the topoisomerase IV (parC). In addition, mutations that render the MexAB-oprM pump (mexR) dysfunctional, leading to its overexpression, also enhance resistance to fluoroquinolones. In this study, we aim to detect point mutations of gyrA, parC, and mexR genes that are predicted to be associated with fluoroquinolone resistance in 141 fluoroquinolone-resistant clinical isolates of P. aeruginosa isolated in Vietnam during 2013–2016.
Methods: We tested minimum inhibitory concentrations (MICs) of fluoroquinolone antibiotics in 141 clinical isolates of P. aeruginosa using the VITEK 2 Compact System, followed by PCR assay, to detect and clone the fluoroquinolone resistance-determining region (FRDR) of gyrA, parC, and mexR. Point mutations were analyzed through Sanger sequencing, and the correlation between genetic mutations and phenotypic resistance of 141 clinical isolates was undertaken.
Results: Fluoroquinolone-resistant substitution mutations such as Ile for Thr83 and Met for Thr133 in gyrA, Leu for Ser87 in parC, and Val for Glu126 in the repressor of mexR were mainly detected. Comparative analytical data indicated that amino acid alterations within the gyrA and parC genes are highly associated with resistance to ciprofloxacin (CIP) and levofloxacin (LEV) in the isolates, whereas alterations in the efflux regulatory mexR gene are not highly consistent with resistance in these isolates. Moreover, fluoroquinolone-resistant clinical isolates of P. aeruginosa were mainly isolated from pus and sputum specimens.
Conclusion: In clinical isolates of P. aeruginosa, a high correlation was observed between MICs of CIP and LEV and alterations in gyrA and parC genes. However, mutations occurring in mexR did not highly correlate with the antibiotic resistance of the bacterium.

Keywords: fluoroquinolone-resistant Pseudomonas aeruginosa, fluoroquinolone resistance-determining region, FRDR, mutation, gyrA, parC, mexR

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