This research will be done primarily in Mexico City at the Institute Mexicano del Seguro Social in collaboration with Dr. Javier Torres as an extension of NIH grant # R01AI42081. Helicobacter pylori is an important human pathogen that causes peptic ulcer and gastric cancer, which is the second most common cause of cancer mortality worldwide and is especially common in Mexico and other developing countries. One of the most important questions in the pathobiology of H. pylori is why do some infected patients develop disease while others do not? Genomic diversity among bacterial strains partially explains the differences in clinical outcome. For example, disease occurs more commonly in patients infected with H. pylori strains that have the Gag pathogenicity island (PAI). We hypothesize that not only the presence of the PAI but also quantitative differences in expression of PAI and other virulence genes may be associated with the development of disease. We therefore propose to quantitate in vivo bacterial gene expression in H. py/or/-infected patients with asymptomatic gastritis, and compare it to that in patients with peptic ulcer and gastric cancer. Gastric biopsies for culture and RNA extraction will be obtained from approximately 25 H. py/or/- infected patients in each group. Expression of genes on the Cag PAI and selected other virulence genes will be measured directly from gastric biopsies using quantitative real-time RT-PCR. Acquisiton of patient samples, experimental procedures, and data analysis will be performed in the Torres lab with technical support from the Solnick lab, which is currently funded by NIAID to perform in vivo quantitative transcript profiling of H. pylori expression in experimentally infected rhesus macaques. The research proposed here is a direct extension of that work into H. py/or/-infected humans with a well-characterized gastric histopathology. This will provide for the first time a quantitative profile of H. py/or/gene expression in humans with different clinical outcomes, and may have implications for understanding the mechanisms by which H. pylori causes disease. Furthermore, the expertise acquired by the Torres lab can subsequently be applied more broadly to larger patient populations on a genome-wide scale, as well as to other infectious diseases that are important public health threats in Mexico and throughout Latin America.
| Aviles-Jimenez, Francisco; Reyes-Leon, Adriana; Nieto-Patlan, Erik et al. (2012) In vivo expression of Helicobacter pylori virulence genes in patients with gastritis, ulcer, and gastric cancer. Infect Immun 80:594-601 |
