RESUMO
Genes encoding glycosyltransferases can be under relatively high selection pressure, likely due to the involvement of the glycans synthesized in host-microbe interactions. Here, we used mice as an experimental model system to investigate whether loss of α-1,3-galactosyltransferase gene (GGTA1) function and Galα1-3Galß1-4GlcNAcß1-R (αGal) glycan expression affects host-microbiota interactions, as might have occurred during primate evolution. We found that Ggta1 deletion shaped the composition of the gut microbiota. This occurred via an immunoglobulin (Ig)-dependent mechanism, associated with targeting of αGal-expressing bacteria by IgA. Systemic infection with an Ig-shaped microbiota inoculum elicited a less severe form of sepsis compared to infection with non-Ig-shaped microbiota. This suggests that in the absence of host αGal, antibodies can shape the microbiota towards lower pathogenicity. Given the fitness cost imposed by bacterial sepsis, we infer that the observed reduction in microbiota pathogenicity upon Ggta1 deletion in mice may have contributed to increase the frequency of GGTA1 loss-of-function mutations in ancestral primates that gave rise to humans.
Assuntos
Bactérias/metabolismo , Evolução Molecular , Microbioma Gastrointestinal , Intestinos/microbiologia , Polissacarídeos/metabolismo , Primatas/microbiologia , Animais , Bactérias/imunologia , Bactérias/patogenicidade , Feminino , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Interações Hospedeiro-Patógeno , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Mutação com Perda de Função , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Polissacarídeos/imunologia , Primatas/genética , Primatas/imunologia , Primatas/metabolismo , Seleção Genética , Sepse/genética , Sepse/imunologia , Sepse/metabolismo , Sepse/microbiologiaRESUMO
The mammalian gut microbiota harbors a diverse ecosystem where hundreds of bacterial species interact with each other and their host. Given that bacteria use signals to communicate and regulate group behaviors (quorum sensing), we asked whether such communication between different commensal species can influence the interactions occurring in this environment. We engineered the enteric bacterium, Escherichia coli, to manipulate the levels of the interspecies quorum sensing signal, autoinducer-2 (AI-2), in the mouse intestine and investigated the effect upon antibiotic-induced gut microbiota dysbiosis. E. coli that increased intestinal AI-2 levels altered the composition of the antibiotic-treated gut microbiota, favoring the expansion of the Firmicutes phylum. This significantly increased the Firmicutes/Bacteroidetes ratio, to oppose the strong effect of the antibiotic, which had almost cleared the Firmicutes. This demonstrates that AI-2 levels influence the abundance of the major phyla of the gut microbiota, the balance of which is known to influence human health.