Antibacterial activity of ethoxzolamide against Helicobacter pylori strains SS1 and 26695

Mohammad M. Rahman, Alexandra Tikhomirova, Joyanta K. Modak, Melanie L. Hutton, Claudiu Trandafir Supuran, Anna Roujeinikova

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7 Citations (Scopus)

Abstract

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 Helicobacter pylori in vitro via an, as yet, unknown mechanism. To date, EZA activity and resistance have been investigated for only one H. pylori strain, P12. We have now performed a susceptibility and resistance study with H. pylori 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 10-8. 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-H. pylori drug.

Original languageEnglish
Article number20
Number of pages7
JournalGut Pathogens
Volume12
Issue number1
DOIs
Publication statusPublished - 15 Apr 2020

Keywords

  • Ethoxzolamide
  • Genome sequencing
  • Mutation frequency
  • Resistance

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