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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 signaling axis. Together, these findings suggest that conflicts with diarrheal pathogens have had far-reaching impacts on the evolution of mammalian gut physiology.

SUBMITTER: Carey CM 

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

REPOSITORIES: biostudies-literature

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

Carey Clayton M CM   Apple Sarah E SE   Hilbert Zoë A ZA   Kay Michael S MS   Elde Nels C NC  

Cell host & microbe 20210805 9


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  ...[more]

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