Antibiotic resistance in Helicobacter pylori is increasing rapidly and emerging as a major factor in treatment failure. We aimed to identify genetic mutations associated with resistance to clarithromycin (23S rRNA peptidyl transferase), fluoroquinolones (gyrA), and metronidazole (rdxA), and to explore their mechanisms of action through molecular modeling. H. pylori detection and the molecular characterization of genes were conducted directly on gastric biopsies by real-time PCR followed by nucleotide sequencing. A 3D model was used to evaluate molecular interactions between the antibiotics and respective target proteins. H. pylori was identified in 66.7% of 33 patients. An analysis of 23SrRNA revealed novel mutations that, by in silico analysis, do not appear to contribute to clarithromycin resistance. In gyrA, mutations in amino acid residues 87 and 91 had an incidence of 27%, and the in silico analysis revealed that these positions are relevant in the binding and resistance to fluoroquinolones. It is also reported for other mutations, some of which are never described. All rdxA mutations were missense, with R16H, M56V, H97T, G98S, A118T, V123T, and R131K predicted by in silico analysis to impact metronidazole resistance. Monitoring H. pylori gene mutations is crucial for tailoring effective antibiotic therapies. Our study advances personalized medicine by introducing novel methods to detect resistance-related mutations and uncovering the molecular mechanisms driving this resistance.

The aim of the study was to evaluate the activity of three cranberry (Vaccinium macrocarpon) ethanol solutions on Helicobacter pylori growth and urease activity. We included numerous clinical Helicobacter pylori isolates and three methods: agar well diffusion method (AWDM), disk diffusion method (DDM) and urease inhibition test (UIT). The results were expressed as differences in inhibitory zone diameters (AWDM and DDM) or urease inhibition duration (UIT) by cranberry solutions compared to the ethanol control. AWDM showed that 400, 40 and 4 mg/l cranberry extracts inhibited the growth of 82.1, 57.1 and 42.8% of the isolates, respectively, while DDM at the highest cranberry concentration suppressed only 39.3% of the isolates. At 400, 40 and 4 mg/l, cranberry extracts also inhibited urease activity of 63.6, 54.5 and 40.9% isolates within 10 min, but of fewer isolates (18.2, 13.6 and 9.1%, respectively) at the 45th min. Although cranberry activity was dose- and strain-dependent, it affected more than half of the isolates at the two highest concentrations. DDM was less effective in detecting this activity. The cranberry extracts also inhibited the urease activity of H. pylori; however, in most cases, the inhibition was only temporary. Briefly, the high cranberry activity against H. pylori, together with its anti-adhesive, antioxidant, anti-biofilm and anti-cancer properties, justifies its use for prophylaxis or adjunctive treatment of chronic H. pylori infection. Importantly, UIT results suggest the benefit of regular cranberry intake over random intake.