UC Santa Cruz

Helicobacter pylori is a chronic gastric pathogen that infects 3.8 billion people, approximately half the world’s population. All infected individuals develop chronic and unresolved inflammation, but only a subset develop ulcers and gastric cancer. It is not well understood why only certain individuals develop disease while others only experience mild inflammation. Severe inflammation increases the likelihood that an individual develops an ulcer or cancer, making it critical to understand how H. pylori causes inflammation. Recent evidence suggests that gland colonization may control the host inflammatory response to bacterial infections. Factors that regulate gland colonization are limited but bacterial chemotaxis and motility seem to be important for this process in many pathogens. Therefore, we sought to further understand how chemotaxis and motility regulate gastric gland colonization by characterizing how AI-2 sensing via chemoreceptor TlpB affects gland colonization. Our results suggest AI-2 sensing via chemoreceptor TlpB regulates H. pylori’s ability to spread between glands. AI-2 is a class of bacterial quorum sensing molecule. Interestingly, emerging evidence suggests that AI-2 can not only be sensed by bacteria, but also by mammalian cells and can modulate host immune responses. Our results suggest AI-2 can modulate gastric epithelial cell ability to produce various cytokines and that H. pylori mutants that cannot produce AI-2 (luxS) also modulate gastric epithelial cell ability to produce various cytokines. luxS mutants also affected cytokine production in a murine model of infection, ultimately leading to a heightened immune response. Ultimately, the information from this work will allow us to develop novel therapies to treat the underlying inflammation during H. pylori infection.