This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: Helicobacter pylori is a bacterium that commonly infects the stomach, where it causes inflammation (gastritis) in all individuals and peptic ulcer disease or gastric cancer in some. The most intensively studied bacterial factor associated with the development of gastric cancer and peptic ulcer is the cytotoxin-associated gene pathogenicity island (cag PAI). While the cell biology of the H. pylori cag PAI has been studied extensively in vitro, its effects in vivo are poorly understood. We recently used the rhesus macaque model to demonstrate that H. pylori induces an antimicrobial host response in a cag PAI-dependent manner, which includes up-regulation of a suite of innate immune effectors molecules in the gastric mucosa. While it seems paradoxical that H. pylori would carry a genetic element that stimulates anti-bacterial host defenses, it is possible that H. pylori is more resistant to these effectors than other gastric inhabitants, and thus enjoys a competitive advantage in the inflamed stomach. Conversely, interactions between an established microbial community and the host may modulate successful colonization by H. pylori. Our specific goals are to: (a) characterize the microbial community of the stomach in the rhesus macaque and compare the effects of infection with wild-type H. pylori or its isogenic cag PAI knockout, and (b) determine the effects of reducing the gastric microbial community on infection with H. pylori. These studies will contribute to our understanding of the interplay between the host and resident microbiota, as well as antagonistic relationships between members of microbial communities, which may intensify or mitigate the impact of a pathogen on the host.
Showing the most recent 10 out of 408 publications
