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Glycan-based shaping of the microbiota during primate evolution

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) funct...

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Autores principales: Singh, Sumnima, Bastos-Amador, Patricia, Thompson, Jessica Ann, Truglio, Mauro, Yilmaz, Bahtiyar, Cardoso, Silvia, Sobral, Daniel, Soares, Miguel P
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133779/
https://www.ncbi.nlm.nih.gov/pubmed/34009123
http://dx.doi.org/10.7554/eLife.67450
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author Singh, Sumnima
Bastos-Amador, Patricia
Thompson, Jessica Ann
Truglio, Mauro
Yilmaz, Bahtiyar
Cardoso, Silvia
Sobral, Daniel
Soares, Miguel P
author_facet Singh, Sumnima
Bastos-Amador, Patricia
Thompson, Jessica Ann
Truglio, Mauro
Yilmaz, Bahtiyar
Cardoso, Silvia
Sobral, Daniel
Soares, Miguel P
author_sort Singh, Sumnima
collection PubMed
description 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 Galα1-3Galβ1-4GlcNAcβ1-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.
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spelling pubmed-81337792021-05-21 Glycan-based shaping of the microbiota during primate evolution Singh, Sumnima Bastos-Amador, Patricia Thompson, Jessica Ann Truglio, Mauro Yilmaz, Bahtiyar Cardoso, Silvia Sobral, Daniel Soares, Miguel P eLife Evolutionary Biology 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 Galα1-3Galβ1-4GlcNAcβ1-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. eLife Sciences Publications, Ltd 2021-05-19 /pmc/articles/PMC8133779/ /pubmed/34009123 http://dx.doi.org/10.7554/eLife.67450 Text en © 2021, Singh et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Evolutionary Biology
Singh, Sumnima
Bastos-Amador, Patricia
Thompson, Jessica Ann
Truglio, Mauro
Yilmaz, Bahtiyar
Cardoso, Silvia
Sobral, Daniel
Soares, Miguel P
Glycan-based shaping of the microbiota during primate evolution
title Glycan-based shaping of the microbiota during primate evolution
title_full Glycan-based shaping of the microbiota during primate evolution
title_fullStr Glycan-based shaping of the microbiota during primate evolution
title_full_unstemmed Glycan-based shaping of the microbiota during primate evolution
title_short Glycan-based shaping of the microbiota during primate evolution
title_sort glycan-based shaping of the microbiota during primate evolution
topic Evolutionary Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133779/
https://www.ncbi.nlm.nih.gov/pubmed/34009123
http://dx.doi.org/10.7554/eLife.67450
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