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Diarrheal pathogens trigger rapid evolution of the guanylate cyclase-C signaling axis in bats
- Source :
- Cell Host Microbe
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
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.
- Subjects :
- Diarrhea
Sodium-Hydrogen Exchangers
Bacterial Toxins
Cystic Fibrosis Transmembrane Conductance Regulator
Receptors, Enterotoxin
Cyclic GMP-Dependent Protein Kinase Type II
Enterotoxin
Biology
Microbiology
Article
Pathogenesis
Enterotoxins
chemistry.chemical_compound
Chiroptera
Virology
Genetic variation
Animals
Enterotoxigenic Escherichia coli
Natriuretic Peptides
Receptor
Cyclic GMP
Vibrio cholerae
Genetics
Phylogenetic tree
Host (biology)
biology.organism_classification
Enterocytes
chemistry
Guanylate Cyclase
Parasitology
Bacteria
Protein Binding
Signal Transduction
Uroguanylin
Subjects
Details
- ISSN :
- 19313128
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Cell Host & Microbe
- Accession number :
- edsair.doi.dedup.....47336a62ead7be3b79d5eda252f14923