Persistent stomach infection with the bacterium Helicobacter pylori is associated with gastric ulcers and cancer. To gain further insight into the pathology of these diseases, Akada et al. explore the relationship between two main H. pylori virulence factors –CagA and VacA – using genome-wide screening in yeast and validation experiments in human gastric epithelial cells. The data suggest that H. pylori injects CagA into the host cells to which it is attached, inhibiting clathrin-independent endocytosis, preventing the entry of highly cytotoxic VacA into the cells. Instead, secreted VacA might damage distant host cells. This functional antagonism between CagA and VacA allows H. pylori to create a niche for persistence by protecting cells in the immediate microenvironment.
