Anti-Helicobacter pylori activity of ethoxzolamide

Joyanta K. Modak, Alexandra Tikhomirova, Rebecca J. Gorrell, Mohammad M. Rahman, Despina Kotsanas, Tony M. Korman, Jose Garcia-Bustos, Terry Kwok, Richard L. Ferrero, Claudiu T. Supuran, Anna Roujeinikova

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

Ethoxzolamide (EZA), acetazolamide, and methazolamide are clinically used sulphonamide drugs designed to treat non-bacteria-related illnesses (e.g. glaucoma), but they also show antimicrobial activity against the gastric pathogen Helicobacter pylori. EZA showed the highest activity, and was effective against clinical isolates resistant to metronidazole, clarithromycin, and/or amoxicillin, suggesting that EZA kills H. pylori via mechanisms different from that of these antibiotics. The frequency of single-step spontaneous resistance acquisition by H. pylori was less than 5 × 10-9, showing that resistance to EZA does not develop easily. Resistance was associated with mutations in three genes, including the one that encodes undecaprenyl pyrophosphate synthase, a known target of sulphonamides. The data indicate that EZA impacts multiple targets in killing H. pylori. Our findings suggest that developing the approved anti-glaucoma drug EZA into a more effective anti-H. pylori agent may offer a faster and cost-effective route towards new antimicrobials with a novel mechanism of action.
Original languageEnglish
Pages (from-to)1660-1667
Number of pages8
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume34
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Keywords

  • ethoxzolamide
  • genome sequencing
  • MIC/MBC
  • Mutation frequency

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