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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1464484
This article is part of the Research Topic Innovation in Tackling the Global Challenge of Eradicating Antibiotic-Resistant Microorganisms View all articles

The effect of three urease inhibitors on H. pylori viability, urease activity and urease gene expression

Provisionally accepted
Hanaa Shaalan Hanaa Shaalan 1,2Maya Azrad Maya Azrad 1Avi Peretz Avi Peretz 1,2*
  • 1 The Baruch Padeh Medical Center, Poriya, Poriah, Israel
  • 2 Faculty of Medicine, Bar-Ilan University, Safed, Tel Aviv, Israel

The final, formatted version of the article will be published soon.

    Treatment of Helicobacter pylori (H. pylori) infections is challenged by antibiotic resistance. The urease enzyme contributes to H. pylori colonization in the gastric acidic environment by producing a neutral microenvironment. We hypothesized that urease inhibition could affect H. pylori viability. This work aimed to assess the effects of acetohydroxamic acid (AHA), ebselen and baicalin on urease activity, bacterial viability and urease genes expression in H. pylori isolates.Forty-nine H. pylori clinical isolates were collected. Urease activity was assessed using the phenol red method. The urease inhibition assay assessed inhibitors' effects on urease activity. Flow cytometry assessed the effect of inhibitors on bacterial viability. Real time PCR was used to compare urease genes expression levels following urease inhibition.Urease activity levels differed between isolates. Acetohydroxamic acid inhibited urease activity at a concentration of 2.5 mM. Although baicalin inhibited urease activity at lower concentrations, major effects were seen at 8 mM. Ebselen's major inhibition was demonstrated at 0.06 mM. Baicalin (8 mM) significantly reduced ATP production compared to untreated isolates. Baicalin, ebselen and acetohydroxamic acid significantly reduced H. pylori viability. Increased urease genes expression was detected after exposure to all urease inhibitors.In conclusion, higher concentrations of baicalin were needed to inhibit urease activity, compared to acetohydroxamic acid and ebselen. Baicalin, ebselen and acetohydroxamic acid reduced H. pylori viability. Therefore, these inhibitors should be further investigated as alternative treatments for H. pylori infection.

    Keywords: Helicobacter pylori, Urease inhibitors, Urease activity, Bacterial viability, Urease Genes

    Received: 14 Jul 2024; Accepted: 28 Oct 2024.

    Copyright: © 2024 Shaalan, Azrad and Peretz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Avi Peretz, The Baruch Padeh Medical Center, Poriya, Poriah, 15208, Israel

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