Antibacterial activity of ethoxzolamide against Helicobacter pylori strains SS1 and 26695

• Published in: Gut pathogens Vol. 12; no. 1; p. 20
• Main Authors: Rahman, Mohammad M, Tikhomirova, Alexandra, Modak, Joyanta K, Hutton, Melanie L, Supuran, Claudiu T, Roujeinikova, Anna
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.04.2020; BioMed Central; BMC
• Subjects: Antibacterial activity; Antibacterial agents; Antibiotics; Antimicrobial agents; Antiulcer agents; Cell walls; Diuretics; Drug approval; Drug discovery; Drug therapy; Ethoxzolamide; FDA approval; Gene expression; Genome sequencing; Genomes; Genomics; Glaucoma; Helicobacter pylori; Lymphoma; Metronidazole; Microbial drug resistance; Mutation; Mutation frequency; Pathogens; R&D; Research & development; Resistance; RNA polymerase; Short Report; Strains (organisms); Studies; Tetracyclines; Ulcers; Resistance; Genome sequencing; Mutation frequency; Ethoxzolamide
• ISSN: 1757-4749; 1757-4749
• DOI: 10.1186/s13099-020-00358-5

With the rise of bacterial resistance to conventional antibiotics, re-purposing of Food and Drug Administration (FDA) approved drugs currently used to treat non-bacteria related diseases as new leads for antibacterial drug discovery has become an attractive alternative. Ethoxzolamide (EZA), an FDA-approved diuretic acting as a human carbonic anhydrase inhibitor, is known to kill the gastric pathogenic bacterium in vitro via an, as yet, unknown mechanism. To date, EZA activity and resistance have been investigated for only one strain, P12. We have now performed a susceptibility and resistance study with strains SS1 and 26695. Mutants resistant to EZA were isolated, characterized and their genomes sequenced. Resistance-conferring mutations were confirmed by backcrossing the mutations into the parent strain. As with P12, resistance to EZA in strains SS1 and 26695 does not develop easily, since the rate of spontaneous resistance acquisition was less than 10 . Acquisition of resistance was associated with mutations in 3 genes in strain SS1, and in 6 different genes in strain 26695, indicating that EZA targets multiple systems. All resistant isolates had mutations affecting cell wall synthesis and control of gene expression. EZA's potential for treating duodenal ulcers has already been demonstrated. Our findings suggest that EZA may be developed into a novel anti- drug.