Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles

香芹酚和百里酚对幽门螺杆菌碳酸酐酶的选择性抑制可能会损害生物膜的产生和外膜囊泡的释放

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作者:Rossella Grande, Simone Carradori, Valentina Puca, Irene Vitale, Andrea Angeli, Alessio Nocentini, Alessandro Bonardi, Paola Gratteri, Paola Lanuti, Giuseppina Bologna, Pasquale Simeone, Clemente Capasso, Viviana De Luca, Claudiu T Supuran

Abstract

Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance.

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