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J Enzyme Inhib Med Chem. 2019 Dec;34(1):1660-1667. doi: 10.1080/14756366.2019.1663416.

Anti-Helicobacter pylori activity of ethoxzolamide.

Author information

1
Department of Microbiology, Monash University , Clayton , Australia.
2
Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University , Clayton , Australia.
3
Department of Biochemistry and Molecular Biology, Monash University , Clayton , Australia.
4
Monash Infectious Diseases, Monash University, Monash Health , Australia.
5
Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research , Clayton , Australia.
6
Laboratorio di Chimica Bioinorganica, Polo Scientifico, Università degli Studi di Firenze , Sesto Fiorentino , Italy.
7
Neurofarba Department, Sezione di Scienze Farmaceutiche, Università degli Studi di Firenze , Sesto Fiorentino , Italy.

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.

KEYWORDS:

MIC/MBC; Mutation frequency; ethoxzolamide; genome sequencing

PMID:
31530039
DOI:
10.1080/14756366.2019.1663416
Free PMC Article

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