Antimicrobial peptide SAAP-148 inhibits Helicobacter pylori and is associated with membrane disruption, biofilm suppression, and reduced cell-associated urease activity.

AIMS: To investigate the in vitro antibacterial activity and related phenotypic effects of the novel antimicrobial peptide SAAP-148 against Helicobacter pylori (H. pylori).

MATERIALS AND

METHODS

The minimum inhibitory concentration (MIC) of SAAP-148 against H. pylori strains, including multidrug-resistant isolates, was determined using the broth microdilution method. Its activity after short-term exposure to pH-adjusted conditions and its cytotoxicity toward gastric epithelial cells were evaluated. The effects of SAAP-148 on cell morphology, membrane permeability, established biofilms, bacterial viability, cell-associated urease activity, and ureA/ureB gene expression were assessed. Antibacterial activity against one four-drug-resistant H. pylori clinical isolate was further evaluated by colony counting and OD600 measurement.

RESULTS

SAAP-148 exhibited potent antibacterial activity against H. pylori strains with different resistance profiles, with MIC values ranging from 16-32 µg/mL. SAAP-148 retained antibacterial activity after short-term exposure to pH-adjusted conditions and showed low cytotoxicity toward gastric epithelial cells. SAAP-148 treatment was associated with bacterial morphological damage, increased inner and outer membrane permeability, reduced biofilm biomass and biofilm-associated protein content, decreased cell-associated urease activity, and reduced ureA/ureB mRNA expression. In the dedicated MDR model, SAAP-148 also reduced viable counts of one four-drug-resistant H. pylori clinical isolate.

CONCLUSION

SAAP-148 demonstrated promising in vitro activity against H. pylori and was associated with membrane disruption, antibiofilm effects, and reduced urease-associated readouts. These findings support further preclinical evaluation of SAAP-148 as a potential antimicrobial strategy against difficult-to-eradicate H. pylori.