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Interaction of the plasmid-encoded quinolone resistance protein QnrB19 with Salmonella Typhimurium DNA gyrase

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Title: Interaction of the plasmid-encoded quinolone resistance protein QnrB19 with Salmonella Typhimurium DNA gyrase
Authors: Pachanon, Ruttana Browse this author
Koide, Kentaro Browse this author
Kongsoi, Siriporn Browse this author
Nakajima, Chie Browse this author →KAKEN DB
Kapalamula, Thoko Flav Browse this author
Suthienkul, Orasa Browse this author
Suzuki, Yasuhiko Browse this author →KAKEN DB
Keywords: PMQR
Quinolone resistance
Salmonella typhimurium
DNA gyrase
Issue Date: 1-Nov-2020
Publisher: Elsevier
Journal Title: Journal of infection and chemotherapy
Volume: 26
Issue: 11
Start Page: 1139
End Page: 1145
Publisher DOI: 10.1016/j.jiac.2020.06.002
Abstract: Background: Plasmid-encoded quinolone resistance protein Qnr is an important factor in bacterial resistance to quinolones. Qnr interacts with DNA gyrase and reduces susceptibility to quinolones. The gene qnr likely spreads rapidly among Enterobacteriaceae via horizontal gene transfer. Though the vast amounts of epidemiological data are available, molecular details of the contribution of QnrB19, the predominant Qnr in Salmonella spp., to the acquisition of quinolone resistance has not yet been understood well. Objective: We aimed to examine the role of QnrB19 in quinolone resistance acquisition using recombinant Salmonella Typhimurium DNA gyrases and QnrB19. Materials and methods: Recombinant QnrB19 was expressed in E. coli and purified by Ni-NTA agarose column chromatography. DNA supercoiling activities of recombinant Salmonella Typhimurium DNA gyrase were assessed with or without QnrB19 under the existence of three quinolones to measure IC(50)s, the concentration of each quinolone required for 50% inhibition in vitro. Results: The IC(50)s of norfloxacin, ciprofloxacin and nalidixic acid against DNA gyrases were measured to be 0.30, 0.16 and 17.7 mu g/mL, respectively. The addition of QnrB19 increased the IC(50)s of norfloxacin and ciprofloxacin to be 0.81 and 0.48 mu g/mL, respectively, where no effect of QnrB19 was observed on the IC50 of nalidixic acid. Conclusion: QnrB19 was shown for the first time in vitro to have ability to grant non-classical quinolone resistance to S. Typhimurium DNA gyrase. Structural insight on quinolones in this study may contribute to investigate drugs useful for preventing the spread of plasmid carrying PMQR along with other factors associating with antimicrobial resistance in S. Typhimurium and other bacteria. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Rights: © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
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)
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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