The effect of three urease inhibitors on viability, urease activity and urease gene expression.
作者信息
Shaalan Hanaa, Azrad Maya, Peretz Avi
机构信息
The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
Clinical Microbiology Laboratory, Tzafon Medical Center, Poriya, Israel, Affiliated with Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.
出版信息
Front Microbiol. 2024 Nov 15;15:1464484. doi: 10.3389/fmicb.2024.1464484. eCollection 2024.
BACKGROUND
Treatment of () infections is challenged by antibiotic resistance. The urease enzyme contributes to colonization in the gastric acidic environment by producing a neutral microenvironment. We hypothesized that urease inhibition could affect 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 isolates.
METHODS
Forty-nine 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.
RESULTS
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 viability. Increased urease genes expression was detected after exposure to all urease inhibitors.
DISCUSSION
In conclusion, higher concentrations of baicalin were needed to inhibit urease activity, compared to acetohydroxamic acid and ebselen. Baicalin, ebselen and acetohydroxamic acid reduced viability. Therefore, these inhibitors should be further investigated as alternative treatments for infection.