Anti-<i>Helicobacter pylori</i> activity of ethoxzolamide

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 <i>Helicobacter pylori.</i> EZA showed the highest activity, and was effective against clinical isolates resistant to metronidazole, clarithromycin, and/or amoxicillin, suggesting that EZA kills <i>H. pylori via</i> mechanisms different from that of these antibiotics. The frequency of single-step spontaneous resistance acquisition by <i>H. pylori</i> 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 <i>H. pylori</i>. Our findings suggest that developing the approved anti-glaucoma drug EZA into a more effective anti-<i>H. pylori</i> agent may offer a faster and cost-effective route towards new antimicrobials with a novel mechanism of action.