In vivo efficacy of acetazolamide in a mouse model of Neisseria gonorrhoeae infection

Microb Pathog. 2022 Mar:164:105454. doi: 10.1016/j.micpath.2022.105454. Epub 2022 Feb 19.

Abstract

Gonococcal infections represent an urgent public health threat worldwide due to the increasing incidence of infections that has been accompanied by an increase in bacterial resistance to most antibiotics. This has resulted in a dwindling number of effective treatment options. Undoubtedly, there is a critical need to develop new, effective anti-gonococcal agents. In an effort to discover new anti-gonococcal therapeutics, we previously identified acetazolamide, a carbonic anhydrase inhibitor, as a novel inhibitor of Neisseria gonorrhoeae. Acetazolamide exhibited potent anti-gonococcal activity in vitro as it inhibited growth of strains of N. gonorrhoeae at concentrations that ranged from 0.5 to 4 μg/mL. The aim of this study was to investigate the in vivo efficacy of acetazolamide in a mouse model of N. gonorrhoeae genital tract infection. Compared to vehicle-treated mice, acetazolamide significantly reduced the gonococcal burden by 90% in the vagina of infected mice after three days of treatment. These results indicate that acetazolamide warrants further investigation as a promising treatment option to supplement the limited pipeline of anti-gonococcal therapeutics.

Keywords: Carbonic anhydrase inhibitors; Drug repurposing; Gonorrhea; Multidrug-resistant Neisseria gonorrhoeae.

MeSH terms

  • Acetazolamide / pharmacology
  • Acetazolamide / therapeutic use
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Disease Models, Animal
  • Female
  • Gonorrhea* / drug therapy
  • Gonorrhea* / microbiology
  • Mice
  • Neisseria gonorrhoeae

Substances

  • Anti-Bacterial Agents
  • Acetazolamide