A Study on the Regulation and Energy Requirements of Helicobacter pylori Motility and Its Inhibitors

The motility conferred by the flagella is necessary for colonization of the gastric mucosa by Helicobacter pylori, a bacterial risk factor for gastric cancer. In this study, we investigated characteristics of H. pylori movement. The motility of H. pylori was observed at a swimming speed of around 70μm/s or more in vitro. The motility was up-regulated by H^+ at a slightly acidic pH (pH 6.0>5.0>4.0 or 7.4). The addition of a proton-ionophore, carbonyl cyanide m-chlorophenyl hydrazone (CCCP), immediately inhibited the H. pylori motility. In contrast, amiloride, monensin, and orthovanadate had little or no effect on the motility. Some agents inhibited the motility without affecting bacterial growth. In human gastric biopsy specimens, two modes of H. pylori flagella morphology were observed: a spiral flagellar bundle consisting of multiple, polar flagella, and a non-spiral flagellar bundle or multiple, unentwined polar flagella. These results demonstrate not only a feature of in vivo H. pylori flagella morphology and motility, but also that the driving force of the H. pylori flagellar motion is, at least in part, the electrochemical proton gradient across the membrane, and a slightly acidic pH (〜pH 6.0) provides the optimal condition for H. pylori movement. A potential benefit of anti-H. pylori motility agents for eradication therapy is discussed.