2024-03-29T07:33:32Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/801222022-11-17T02:08:08Zhdl_2115_20076hdl_2115_597WQ-3810: A new fluoroquinolone with a high potential against fluoroquinolone-resistant Mycobacterium tuberculosisOuchi, YukiMukai, TetsuKoide, KentaroYamaguchi, TomoyukiPark, Jong-HoonKim, HyunYokoyama, KazumasaTamaru, AkiGordon, Stephen V.Nakajima, ChieSuzuki, YasuhikoWQ-3810Fluoroquinolone resistancegyrA mutationsMycobacterium tuberculosisEthambutolSynergistic effect649Fluoroquinolone (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.ElsevierJournal Articleapplication/pdfhttp://hdl.handle.net/2115/80122https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/80122/1/Tuberculosis_120_101891.pdf1472-9792Tuberculosis1201018912020-01enginfo:doi/10.1016/j.tube.2019.101891©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/author