Translational Research Program

Shared Host Genetics and Bacterial Adaptation in the Transmission of H. pylori

Principal Investigator: Sarah Talarico  Mentor: Nina Salama
The proposed research is a study of H. pylori transmission within families and the bacterial genetic changes that occur during adaptation to a new host. H. pylori transmission predominantly occurs within families, but it is not known if this is attributable to the sustained close contacts between family members or because the genetic relatedness of the family members facilitates transmission. Bacterial adaptations to the individual host that occur during H. pylori’s decades-long infection may cause the strain to be better able to colonize a genetically similar host. H. pylori has many mechanisms for genetic diversification, which likely aids the bacterium in adapting to the newly infected host after transmission. Diversification of genes that encode H. pylori cell surface structures that interact with the host is especially likely to be important during adaptation to a new host. In this grant, we test the hypothesis that H. pylori transmission predominantly occurs within families because an H. pylori strain that is adapted to the individual host is better able to colonize a genetically similar host. Furthermore, we test the hypothesis that H. pylori will undergo more genetic diversification when being transmitted between unrelated individuals than between related individuals. Aim 1 proposes to collect stool samples from members of families with biological children and families with adopted children, genotype H. pylori from the stool DNA, and compare the extent of H. pylori genotype sharing, which indicates transmission, between the two different types of families using statistical analysis. In Aim 2, H. pylori DNA isolated from family members who share the same H. pylori strain will be compared by PCR and DNA sequencing to look for genetic changes to genes involved in bacterial-host interactions that would affect expression or function of the encoded protein. The extent of genetic changes within H. pylori strain pairs shared by related and unrelated family members will then be examined. The proposed research will result in important information about the patterns of H. pylori transmission within families and the contribution of shared host genetics versus household contact to transmission. Further knowledge of the factors involved in H. pylori transmission will inform strategies for preventing and treating new infections. The proposed research will also result in an improved understanding of the genetic diversification and adaptation of H. pylori to a new host, allowing the bacteria to maintain an active, persistent infection in the face of host defenses and eventually cause ulcers and stomach cancer.