The bacterium Helicobacter pylori, which lives in the human stomach and is associated with ulcers and gastric cancer, is shaped like a corkscrew, or helix. For years researchers have hypothesized that the bacterium’s twisty shape is what enables it to survive – and thrive – within the stomach’s acid-drenched environment, but until now they have had no proof.
For the first time, researchers at Fred Hutchinson Cancer Research Center have found that, at least when it comes to H. pylori’s ability to colonize the stomach, shape indeed matters. Microbiologist Nina Salama, PhD, and colleagues report their findings May 28 in Cell.
Salama and colleagues are the first to demonstrate that the bug’s helical shape helps it set up shop in the protective gelatin-like mucus that coats the stomach. Such bacterial colonization – present in up to half of the world’s population – causes chronic inflammation that is linked to a variety of stomach disorders, from chronic gastritis and duodenitis to ulcers and cancer.
“By understanding how the bug colonizes the stomach, we can think about targeting therapy to prevent infection in the first place,” said Salama, the paper’s corresponding author and an associate member of the Human Biology Division at the Hutchinson Center. The paper’s first author, Laura K. Sycuro, PhD, conducted this work while a student in the University of Washington/Fred Hutchinson Cancer Research Center Molecular and Cellular Biology graduate program. She is now a postdoctoral research associate in the Hutchinson Center’s Clinical Research Division.
Specifically, the researchers discovered a group of four proteins that are responsible for generating H. pylori’s characteristic curvature. Using a mouse model, they found that laboratory-engineered mutant strains of H. pylori that are deficient in these proteins fail to twist properly and, consequently, are unable to colonize the stomach.
“Having these mutant strains in hand allowed us to test whether the helical shape is important for H. pylori infection, and it is,” Salama said. “All of our mutants had trouble colonizing the stomach and were out-competed by normal, helical-shaped bugs.” Interestingly and somewhat puzzlingly, the H. pylori mutants retained their ability to propel themselves through a thick, mucus-like gel in a petri dish even though they were unable to establish infection in stomach colonization experiments.
