Temporin-SHa and Its Analogs as Potential Candidates for the Treatment of Helicobacter pylori

Abstract

<i>Helicobacter</i><i>pylori</i> is one of the most prevalent pathogens colonizing 50% of the world's population and causing gastritis and gastric cancer. Even with triple and quadruple antibiotic therapies, <i>H. pylori</i> shows increased prevalence of resistance to conventional antibiotics and treatment failure. Due to their pore-forming activity, antimicrobial peptides (AMP) are considered as a good alternative to conventional antibiotics, particularly in the case of resistant bacteria. In this study, temporin-SHa (a frog AMP) and its analogs obtained by Gly to Ala substitutions were tested against <i>H. pylori</i>. Results showed differences in the antibacterial activity and toxicity of the peptides in relation to the number and position of D-Ala substitution. Temporin-SHa and its analog NST1 were identified as the best molecules, both peptides being active on clinical resistant strains, killing 90-100% of bacteria in less than 1 h and showing low to no toxicity against human gastric cells and tissue. Importantly, the presence of gastric mucins did not prevent the antibacterial effect of temporin-SHa and NST1, NST1 being in addition resistant to pepsin. Taken together, our results demonstrated that temporin-SHa and its analog NST1 could be considered as potential candidates to treat <i>H. pylori</i>, particularly in the case of resistant strains.