Helicobacter pylori, a gram negative bacteria that colonize the human stomach, are associated with diseases of the upper gastrointestinal tract. Examination of the selective pressures on H.pylori provide a model for host interactions with resident flora since (I) H.pylori strains are highly diverse, and continued variation is occurring during colonization of a single host; (ii) H.pylori strains lack SOS repair, are naturally competent, and have substantial ability to exchange DNA with other H.pylori cells, providing opportunities for the observed """"""""quasi-species"""""""" development; (iii) H.pylori Lewis expression varies during colonization and host characteristics selected for particular phenotypes; (iv) molecular loci have been identified that are involved in Lewis variation, and mouse models have been developed in which variation can be predictably observed; (v) Mathematical models have been developed for H.pylori colonization in general and the dynamics of Lewis expression can be measured and develop a model to predict its behavior.
The specific aims are (1) To construct an experimental rodent model for assessing population genetic changes in H.pylori during gastric colonization of a single host, and to develop a deterministic mathematical model that is representative and predictive. (2) To assess the effects on variation of prior host phenotype, inoculum size, bacterial mutation rate, and host immunological response on H.pylori population dynamics, phenotypes, and genotypes to better identify the parameters of the mathematical model. (3) To examine the effect of recombination between two different H.pylori strains during experimental infections, and to develop representative mathematical models for this more complex phenomenon.
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