| Title: | WQ-3810: A new fluoroquinolone with a high potential against fluoroquinolone-resistant Mycobacterium tuberculosis |
| Authors: | Ouchi, Yuki Browse this author |
| Mukai, Tetsu Browse this author |
| Koide, Kentaro Browse this author |
| Yamaguchi, Tomoyuki Browse this author |
| Park, Jong-Hoon Browse this author |
| Kim, Hyun Browse this author |
| Yokoyama, Kazumasa Browse this author |
| Tamaru, Aki Browse this author |
| Gordon, Stephen V. Browse this author |
| Nakajima, Chie Browse this author →KAKEN DB |
| Suzuki, Yasuhiko Browse this author →KAKEN DB |
| Keywords: | WQ-3810 |
| Fluoroquinolone resistance |
| gyrA mutations |
| Mycobacterium tuberculosis |
| Ethambutol |
| Synergistic effect |
| Issue Date: | Jan-2020 |
| Publisher: | Elsevier |
| Journal Title: | Tuberculosis |
| Volume: | 120 |
| Start Page: | 101891 |
| Publisher DOI: | 10.1016/j.tube.2019.101891 |
| Abstract: | Fluoroquinolone (FQ) resistance in Mycobacterium tuberculosis (Mtb), caused by amino acid substitutions in DNA gyrase, has been increasingly reported worldwide. WQ-3810 is a newly developed FQ that is highly active against FQ-resistant pathogens; however, its activity against Mtb has not been evaluated. Herein we examined the efficacy of WQ-3810 against Mtb through the use of recombinant Mtb DNA gyrases. In addition, in vitro anti-mycobacterial activity of WQ-3810 was evaluated against recombinant Mtb var. bovis Bacille Calmette-Guerin strains in which gyrase-coding genes were replaced with Mtb variants containing resistance-conferring mutations. WQ-3810 showed a higher inhibitory activity than levofloxacin against most recombinant DNA gyrases with FQ-resistance mutations. Furthermore, WQ-3810 showed inhibition even against a DNA gyrase variant harboring a G88C mutation which is thought to confer the highest resistance against FQs in clinical Mtb isolates. In contrast, the FQ susceptibility test showed that WQ-3810 had relatively weak mycobactericidal activity compared with moxifloxacin. However, the combination of WQ-3810 and ethambutol showed the greatest degree of synergistic activity against recombinant strains. Since FQs and ethambutol have been used in multi-drug therapy for tuberculosis, WQ-3810 might represent a new, potent anti-tuberculosis drug that can be effective even against FQ-resistant Mtb strains. |
| Rights: | ©2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/80122 |
| 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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