H. pylori infection affects more than half of the world population and is a major cause of chronic gastritis, peptic ulcer disease and gastric cancer. Current clinical treatment of H. pylori infection requires a combination of two antibiotics and one proton pump inhibitor. However, the combination treatment suffers from increased drug-resistance and non-selective toxicity to commensal bacteria and host. Antimicrobial peptides are believed to be harder for bacteria to become resistant, but they also lack selectivity between H. pylori and commensal bacteria. Here, we aim to develop a new class of pH-activated antimicrobial polypeptide as a single agent to selectively kill H. pylori while maintaining minimal toxicity to commensal bacteria and host. Specifically, a series of random co-polypeptides were synthesized by ring-opening polymerization of different N-carboxyanhydride (NCA) monomers. They adopt a neutral surface at physiological environment and exhibit very low the toxicity to host and commensal bacteria. However, once entering the acidic gastric environment, these peptides transform into a cationic surface and exhibit potent antimicrobial activity to H. pylori thriving in the stomach. The pH-dependent antimicrobial activity is also confirmed by in vitro study. Moreover, the antimicrobial activity and toxicity will be further tuned through structure-activity studies.

Selective killing of Helicobacter pylori with pH-responsive antimicrobial polypeptides

2019 Fall National Meeting

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