Diarrheal pathogens trigger rapid evolution of the guanylate cyclase-C signaling axis in bats.

ABSTRACT: The pathogenesis of infectious diarrheal diseases is largely attributed to enterotoxins that cause dehydration by disrupting intestinal water absorption. We investigated patterns of genetic variation in mammalian guanylate cyclase-C (GC-C), an intestinal receptor targeted by bacterially encoded heat-stable enterotoxins (STa), to determine how host species adapt in response to diarrheal infections. Our phylogenetic and functional analysis of GC-C supports long-standing evolutionary conflict with diarrheal bacteria in primates and bats, with highly variable susceptibility to STa across species. In bats, we further show that GC-C diversification has sparked compensatory mutations in the endogenous uroguanylin ligand, suggesting an unusual scenario of pathogen-driven evolution of an entire sig

SUBMITTER: Carey CM 

PROVIDER: S-EPMC8429143 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature