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Characterization of Campylobacter jejuni DNA gyrase as the target of quinolones

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/76492

Title: Characterization of Campylobacter jejuni DNA gyrase as the target of quinolones
Authors: Changkwanyeun, Ruchirada Browse this author
Usui, Masaru Browse this author
Kongsoi, Siriporn Browse this author
Yokoyama, Kazumasa Browse this author
Kim, Hyun Browse this author →KAKEN DB
Suthienkul, Orasa Browse this author
Changkaew, Kanjana Browse this author
Nakajima, Chie Browse this author →KAKEN DB
Tamura, Yutaka Browse this author →KAKEN DB
Suzuki, Yasuhiko Browse this author →KAKEN DB
Keywords: DNA gyrase
Quinolones
Campylobacter jejuni
Issue Date: Aug-2015
Publisher: Elsevier
Journal Title: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy
Volume: 21
Issue: 8
Start Page: 604
End Page: 609
Publisher DOI: 10.1016/j.jiac.2015.05.003
PMID: 26096494
Abstract: Quinolones have long been used as the first-line treatment for Campylobacter infections. However, an increased resistance to quinolones has raised public health concerns. The development of new quinolone-based antibiotics with high activity is critical for effective, as DNA gyrase, the target of quinolones, is an essential enzyme for bacterial growth in several mechanisms. The evaluation of antibiotic activity against Campylobacter jejuni largely relies on drug susceptibility tests, which require at least 2 days to produce results. Thus, an in vitro method for studying the activity of quinolones against the C. jejuni DNA gyrase is preferred. To identify potent quinolones, we investigated the interaction of C. jejuni DNA gyrase with a number of quinolones using recombinant subunits. The combination of purified subunits exhibited DNA supercoiling activity in an ATP dependent manner. Drug concentrations that inhibit DNA supercoiling by 50% (IC50s) of 10 different quinolones were estimated to range from 0.4 (sitafloxacin) to >100 µg/mL (nalidixic acid). Sitafloxacin showed the highest inhibitory activity, and the analysis of the quinolone structure-activity relationship demonstrated that a fluorine atom at R-6 might play the important role in the inhibitory activity against C. jejuni gyrase. Measured quinolone IC50s correlated well with minimum inhibitory concentrations (R = 0.9943). These suggest that the in vitro supercoiling inhibition assay on purified recombinant C. jejuni DNA gyrase is a useful and predictive technique to monitor the antibacterial potency of quinolones. And furthermore, these data suggested that sitafloxacin might be a good candidate for clinical trials on campylobacteriosis.
Rights: © 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
https://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/76492
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)
国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 鈴木 定彦

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