A singe polypeptide-based therapy is shown to be effective at targeting Helicobacter pylori without harming helpful gut microbes. Current treatment of an H. pylori infection includes a combination of two or more antibiotics and a proton pump inhibitor. Although this approach is aggressive, it tends to be ineffective due to antibiotic drug resistance. In addition, the depletion of good bacteria is an unwanted side effect.
The study findings were recently published in the Proceedings of the National Academy of Sciences. The paper described that in the acidic pH environment of the stomach, the polymer makes a conformational change from an inactive structure to an active one that kills H. pylori by disrupting its bacterial membrane. The polymer becomes inactive again in the small intestine, which has a higher pH than the stomach. Traditional therapies can kill good gut bacterial by more than 65%. This unique polymer-based approach resulted in minimal toxicity to normal tissues and commensal bacteria.
"This is a very simple solution to this disease," Cheng said. "These materials become therapeutically effective in the stomach, but once they move to the small intestine—whereyou have a lot of good bacteria—the pH is neutral or slightly basic and the materials quickly lose their rigid structures. Then they are excreted from the body."
The research was performed on several mouse cell lines infected with H. pylori. The next step for the team is to replicate the study in large animal models and then potentially perform human studies.
Image: At normal tissue pH (left), the polymer is inactive and does not kill bacteria. But in an acidic environment (right), it disrupts bacterial membranes to kill H. pylori in the stomach. Credit: Image courtesy of Jianjun Cheng, University of Illinois