The human gastric pathogen Helicobacter pylori has infected more than half of the world's population and is therefore an interesting model for gastrointestinal colonization. For successful colonisation, H. pylori must retain active motility in the gastric lumen until it reaches the safety of the mucus layer. We inserted bacteria into the stomach of anaesthetized Mongolian gerbils and adjusted the gastric juice to defined pH values of between 2.0 and 6.0 by using an autotitrator. We found H. pylori loses its motility within one minute at lumen pH values of 2 and 3. At pH 4 motility was lost after 2 minutes and the period of motility increased to more than 15 minutes at pH 6. However, blocking pepsins in the gastric lumen in vivo by using pepstatin, significantly increased the period of motility. We found that the antibacterial effect of pepsin occurs in two phases: the rapid loss of motility and subsequent destruction of the bacteria. It was possible to simulate rapid loss of motility in vitro using pepsin solutions. Using isolated pepsin isoenzymes, we found that the main effect was caused by pepsin C, which has an antibacterial efficiency ten times higher than pepsin A.

We conclude that pepsin limits the persistence of H. pylori in the gastric content in vivo to a few minutes by rapidly inhibiting motility. Therefore, it is likely that inhibition of bacterial motility is an important component of the gastric bactericidal barrier.