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Impact of mutations in DNA gyrase genes on quinolone resistance in Campylobacter jejuni

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Title: Impact of mutations in DNA gyrase genes on quinolone resistance in Campylobacter jejuni
Authors: Changkwanyeun, Ruchirada Browse this author
Yamaguchi, Tomoyuki Browse this author
Kongsoi, Siriporn Browse this author
Changkaew, Kanjana Browse this author
Yokoyama, Kazumasa Browse this author
Kim, Hyun Browse this author
Suthienkul, Orasa Browse this author
Usui, Masaru Browse this author
Tamura, Yutaka Browse this author →KAKEN DB
Nakajima, Chie Browse this author →KAKEN DB
Suzuki, Yasuhiko Browse this author →KAKEN DB
Keywords: Campylobacter jejuni
quinolone resistance
DNA gyrase
Issue Date: Oct-2016
Publisher: Wiley-Blackwell
Journal Title: Drug Testing and Analysis
Volume: 8
Issue: 10
Start Page: 1071
End Page: 1076
Publisher DOI: 10.1002/dta.1937
PMID: 26857529
Abstract: Amino acid substitutions providing quinolone resistance to Campyloabcter jejuni have been found in the quinolone resistance-determining region of protein DNA gyrase subunit A (GyrA), with the highest frequency at position 86 followed by position 90. In this study, wild-type and mutant recombinant DNA gyrase subunits were expressed in Escherichia coli and purified using Ni-NTA agarose column chromatography. Soluble 97 kDa GyrA and 87 kDa DNA gyrase subunit B were shown to reconstitute ATP-dependent DNA supercoiling activity. A quinolone-inhibited supercoiling assay demonstrated the roles of Thr86Ile, Thr86Ala, Thr86Lys, Asp90Asn, and Asp90Tyr amino acid substitutions in reducing sensitivity to quinolones. The marked effect of Thr86Ile on all examined quinolones suggested the advantage of this substitution in concordance with recurring isolation of quinolone-resistant C. jejuni. An analysis of the structure-activity relationship showed the importance of the substituent at position 8 in quinolones to overcome the effect of Thr86Ile. Sitafloxacin (SIT), which has a fluorinate cyclopropyl ring at R-1 and a chloride substituent at R-8, a characteristic not found in other quinolones, showed the highest inhibitory activity against all mutant C. jejuni gyrases including ciprofloxacin-resistant mutants. The results suggest SIT as a promising drug for the treatment of campylobacteriosis caused by CIP-resistant C. jejuni. Copyright (C) 2016 John Wiley & Sons, Ltd.
Rights: This is the peer reviewed version of the following article: R. Changkwanyeun, T. Yamaguchi, S. Kongsoi, K. Changkaew, K. Yokoyama, H. Kim, O. Suthienkul, M. Usui, Y. Tamura, C. Nakajima, Y. Suzuki. Impact of mutations in DNA gyrase genes on quinolone resistance in Campylobacter jejuni. Drug Test. Anal. 2016, 8, 1071, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Type: article (author version)
Appears in Collections:人獣共通感染症リサーチセンター (Research Center for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 鈴木 定彦

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