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WQ-3810 inhibits DNA gyrase activity in ofloxacin-resistant Mycobacterium leprae

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Title: WQ-3810 inhibits DNA gyrase activity in ofloxacin-resistant Mycobacterium leprae
Authors: Park, Jong-Hoon Browse this author
Yamaguchi, Tomoyuki Browse this author
Ouchi, Yuki Browse this author
Koide, Kentaro Browse this author
Mori, Shigetarou Browse this author
Kim, Hyun Browse this author
Mukai, Tetsu Browse this author
Nakajima, Chie Browse this author
Suzuki, Yasuhiko Browse this author →KAKEN DB
Keywords: Mycobacterium leprae
DNA gyrase
Recombinant molecules
Issue Date: Apr-2020
Publisher: Elsevier
Journal Title: Journal of infection and chemotherapy
Volume: 26
Issue: 4
Start Page: 335
End Page: 342
Publisher DOI: 10.1016/j.jiac.2019.10.013
Abstract: Background: Mycobacterium leprae causes leprosy and ofloxacin is used to control this bacterium. However, specific amino acid substitutions in DNA gyrases of M. leprae interferes with the effect of ofloxacin. Methodology/principal findings: Here we tested the inhibitory effect of WQ-3810 on DNA gyrases in M. leprae, using recombinant gyrases. We theorized that WQ-3810 and DNA gyrases interacted, which was tested in silico. Compared with control drugs like ofloxacin, WQ-3810 showed a better inhibitory effect on ofloxacin-resistant DNA gyrases. The in-silico study showed that, unlike control drugs, a specific linkage between a R1 group in WQ-3810 and aspartic acid at position 464 in the subunit B of DNA gyrases existed, which would enhance the inhibitory effect of WQ-3810. This linkage was confirmed in a further experiment, using recombinant DNA gyrases with amino acid substitutions in subunits B instead. Conclusions/significance: The inhibitory effect of WQ-3810 was likely enhanced by the specific linkage between a R1 group residue in its structure and DNA gyrases. Using interactions like the one found in the present work may help design new fluoroquinolones that contribute to halt the emergence of antibiotic-resistant pathogens. (c) 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Rights: © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections: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)
獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 鈴木 定彦

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