Host-microbe Evolutionary Conflict: Investigating the Host Specificity of Helicobacter pylori Adhesin HopQ Via its Engagement with Primate CEACAM1
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Date
2019
Authors
Brush, Eden Rose
Journal Title
Journal ISSN
Volume Title
Publisher
University of Oregon
Abstract
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 which can contribute to the antagonistic evolution of host and microbial genomes. Specific adhesion to host 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 CEACAM1 proteins are rapidly evolving, suggesting an evolutionary 'arms race' with the bacterial adhesins that target them. One such adhesin is Helicobacter outer protein Q (HopQ) of Helicobacter pylori. H. pylori is a human-specific bacterium that colonizes the stomach of approximately half of the human population worldwide and is the major causative agent for stomach ulcers and gastric cancer. The HopQ gene has two major variants that are associated with both virulence and geographical location. 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 biochemical binding experiments 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, chimpanzee, and gorilla CEACAM1. We also found multiple signatures of positive selection on sites of HopQ that contact rapidly evolving sites on the N domain of CEACAM1 lending support to a potential evolutionary “arms race” between the two. These findings are directly applicable to human health, as understanding the determinants of host specificity in human-associated pathogens could reveal new avenues for the treatment and prevention of infectious diseases as well as provide valuable information about which species are more susceptible to reverse zoonoses, the transfer of a disease-causing agent from humans to non-human animals.
Description
35 pages
Keywords
Biology, Adhesin, Evolutionary Arms Race, Positive Selection, Molecular Evolution, Bacterial Infectionm