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Impact of mutations in DNA gyrase genes on quinolone resistance in Campylobacter jejuni
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 | mutation |
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 http://dx.doi.org/10.1002/dta.1937. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/67280 |
Appears in Collections: | 人獣共通感染症国際共同研究所 (International Institute for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 鈴木 定彦
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