Selective killing of Helicobacter pylori with pH-responsive helix–coil conformation transitionable antimicrobial polypeptides

Significance Clinical treatment of Helicobacter pylori using combination therapy is greatly challenged by the undesired killing of commensal bacteria and progressive development of drug resistance. To address these issues, we developed pH-sensitive, helix–coil conformation transitionable, antimicrobial polypeptides as a single therapeutic agent to selectively kill H. pylori under acidic condition in the stomach with minimal toxicity to commensal bacteria and diminished drug resistance. Through the control of the secondary structure transition, the polypeptides showed unappreciable toxicity to commensal bacteria and tissues at physiological pH when they adopted random coiled conformation, while the restoration of helical structure in the acidic stomach allowed the polypeptide to regain membrane disruptive capability to effectively and selectively kill H. pylori , including drug-resistant strains.