WQ-3810: A new fluoroquinolone with a high potential against fluoroquinolone-resistant Mycobacterium tuberculosis

Yuki Ouchi, Tetsu Mukai, Kentaro Koide, Tomoyuki Yamaguchi, Jong Hoon Park, Hyun Kim, Kazumasa Yokoyama, Aki Tamaru, Stephen V. Gordon, Chie Nakajima, Yasuhiko Suzuki

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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 antimycobacterial activity of WQ-3810 was evaluated against recombinant Mtb var. bovis Bacille Calmette–Guérin 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.

Original languageEnglish
Article number101891
JournalTuberculosis
Volume120
DOIs
Publication statusPublished - Jan 2020
Externally publishedYes

Keywords

  • Ethambutol
  • Fluoroquinolone resistance
  • Mycobacterium tuberculosis
  • Synergistic effect
  • WQ-3810
  • gyrA mutations

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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