Host-microbe evolutionary antagonism in primates: HopQ’s role as a bacterial adhesin targeting CEACAM1

Presenter(s): Eden Brush

Faculty Mentor(s): Matt Barber

Oral Session 1 O

How animals and microbes interact with each other can mean the difference between harmonious coexistence and deadly infection. These interactions create the potential for evolutionary conflict between host and microbial proteins which can contribute to antagonistic evolution of host and microbial genomes. Specific adhesion to host tissue cells is often a necessary first step in bacterial pathogenesis; “adhesins” are proteins on bacterial surfaces that mediate host cell adhesion and subsequently, invasion and infection. The N-domain of human carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a host protein that modulates cell adhesion and other cell processes, is targeted and exploited by various human- associated bacterial adhesins. The Barber Lab at the University of Oregon has recently discovered that primate CEACAM proteins are rapidly evolving, suggesting an evolutionary ‘arms race’ with the bacterial proteins that target them. One such adhesin is HopQ of Helicobacter pylori. H. pylori is a bacterium that colonizes the stomach of ~50% of the human population worldwide and is the major causative agent for stomach ulcers and gastric cancer. It remains unclear how genetic diversity among adhesins such as HopQ impacts host specificity. We tested our hypothesis that HopQ will bind differentially to various primate CEACAM1 proteins by performing pull-down assays and western blots with H. pylori and recombinant, GFP-tagged, CEACAM1 N domains from a panel of primates. Interestingly, we found that HopQ binds to the N domains of human, chimp, and gorilla CEACAM1. We also found multiple sites of positive selection on HopQ that contact rapidly evolving sites in CEACAM1 lending support to a potential evolutionary ‘arms race’ between the two. These findings are directly applicable to human health, as the host specificity of a pathogen can determine what species are more susceptible to reverse zoonosis, the transfer of a disease-causing agent from humans to animals.