Designer peptides treat stomach pathogen

About half the world’s population harbors Helicobacter pylori bacteria, which cause ulcers and cancer. Treatment of symptomatic patients usually involves triple therapy—two antibiotics and an acid reducer—but H. pylori resists some antibiotics. Treatment is also challenging because the pathogens reside in the stomach, where drugs need to tolerate high acidity. Jianjun Cheng and Lin-Feng Chen at the University of Illinois, Urbana-Champaign; Lichen Yin of Soochow University; and coworkers have now developed peptides that not only tolerate acidity but use it to activate their antibacterial activity (Proc. Natl. Acad. Sci. USA 2017, DOI: 10.1073/pnas.1710408114). At low pH, such as in the stomach, the orally administered peptides adopt a positively charged helical conformation that kills bacteria by disrupting their membranes. At the normal physiological pH of the intestines and bloodstream, the peptides transform into a random-coil conformation that doesn’t bind anything in particular very effectively, so they don’t kill “good” intestinal bacteria or hurt body cells. Liangfang Zhang of the University of California, San Diego, comments that in infected mice, the peptides have “impressive anti-H. pylori efficacy, equivalent to that of triple therapy.”