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

Park, Jong-Hoon; Yamaguchi, Tomoyuki; Ouchi, Yuki et al.

Journal of infection and chemotherapy, 2020, 26(4), 335-342

Permalink : https://hdl.handle.net/2115/81104

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アクセス権
open access
URI
https://hdl.handle.net/2115/81104
タイトル
WQ-3810 inhibits DNA gyrase activity in ofloxacin-resistant Mycobacterium leprae
著者
Park, Jong-Hoon ; Yamaguchi, Tomoyuki ; Ouchi, Yuki ; Koide, Kentaro ; Mori, Shigetarou ; Kim, Hyun ; Mukai, Tetsu ; Nakajima, Chie ; Suzuki, Yasuhiko
著者名
Park, Jong-Hoon
著者名
Yamaguchi, Tomoyuki
著者名
Ouchi, Yuki
著者名
Koide, Kentaro
著者名
Mori, Shigetarou
著者名
Kim, Hyun
著者名
Mukai, Tetsu
著者名
Nakajima, Chie
e-Rad_Researcher
90206540
著者名
Suzuki, Yasuhiko
言語
英語
キーワード
Mycobacterium leprae
DNA gyrase
WQ-3810
Recombinant molecules
発行日
2020-04
出版者
Elsevier
収録物名
Journal of infection and chemotherapy
巻(号)
26(4)
ページ
335-342
抄録
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.
資源タイプ
学術雑誌論文
出版タイプ
Accepted Manuscript
権利情報
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN
1341-321X
関連情報 (isVersionOf)
出版社版DOI
https://doi.org/10.1016/j.jiac.2019.10.013