Gut Symbiont <italic toggle="yes">Bacteroides fragilis</italic> Secretes a Eukaryotic-Like Ubiquitin Protein That Mediates Intraspecies Antagonism

ABSTRACT Human gut Bacteroides species produce different types of toxins that antagonize closely related members of the gut microbiota. Some are toxic effectors delivered by type VI secretion systems, and others are non-contact-dependent secreted antimicrobial proteins. Many strains of Bacteroides f...

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Autores principales:	Maria Chatzidaki-Livanis, Michael J. Coyne, Kevin G. Roelofs, Rahul R. Gentyala, Jarreth M. Caldwell, Laurie E. Comstock
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Bacteroides antagonism microbiota ubiquitin Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b82fd22b110442cea1336cccb91552ed
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spelling	oai:doaj.org-article:b82fd22b110442cea1336cccb91552ed2021-11-15T15:51:56ZGut Symbiont <italic toggle="yes">Bacteroides fragilis</italic> Secretes a Eukaryotic-Like Ubiquitin Protein That Mediates Intraspecies Antagonism10.1128/mBio.01902-172150-7511https://doaj.org/article/b82fd22b110442cea1336cccb91552ed2017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01902-17https://doaj.org/toc/2150-7511ABSTRACT Human gut Bacteroides species produce different types of toxins that antagonize closely related members of the gut microbiota. Some are toxic effectors delivered by type VI secretion systems, and others are non-contact-dependent secreted antimicrobial proteins. Many strains of Bacteroides fragilis secrete antimicrobial molecules, but only one of these toxins has been described to date (Bacteroidales secreted antimicrobial protein 1 [BSAP-1]). In this study, we describe a novel secreted protein produced by B. fragilis strain 638R that mediated intraspecies antagonism. Using transposon mutagenesis and deletion mutation, we identified a gene encoding a eukaryotic-like ubiquitin protein (BfUbb) necessary for toxin activity against a subset of B. fragilis strains. The addition of ubb into a heterologous background strain conferred toxic activity on that strain. We found this gene to be one of the most highly expressed in the B. fragilis genome. The mature protein is 84% similar to human ubiquitin but has an N-terminal signal peptidase I (SpI) signal sequence and is secreted extracellularly. We found that the mature 76-amino-acid synthetic protein has very potent activity, confirming that BfUbb mediates the activity. Analyses of human gut metagenomic data sets revealed that ubb is present in 12% of the metagenomes that have evidence of B. fragilis. As 638R produces both BSAP-1 and BfUbb, we performed a comprehensive analysis of the toxin activity of BSAP-1 and BfUbb against a set of 40 B. fragilis strains, revealing that 75% of B. fragilis strains are targeted by one or the other of these two secreted proteins of strain 638R. IMPORTANCE We are just beginning to understand some of the important interactions that occur between microbes of the human gut microbiota that dictate the composition and abundance of its constituent members. The ability of one member to produce molecules that directly kill a coresident member has been shown among minor gut species and is just starting to be studied in the abundant Bacteroides species. Here, we show that some strains of Bacteroides fragilis have acquired a gene encoding a secreted eukaryotic-like ubiquitin protein with potent inhibitory activity against other B. fragilis stains. This is the first bacterially encoded ubiquitin-like molecule shown to function like a bacterial toxin. This molecule is an example of a gut symbiont acquiring and adapting a eukaryotic molecule likely to increase its competitiveness in the mammalian gut. Understanding antagonistic factors produced by abundant gut symbionts is an important prerequisite to properly engineer strains to colonize the gut for health benefits.Maria Chatzidaki-LivanisMichael J. CoyneKevin G. RoelofsRahul R. GentyalaJarreth M. CaldwellLaurie E. ComstockAmerican Society for MicrobiologyarticleBacteroidesantagonismmicrobiotaubiquitinMicrobiologyQR1-502ENmBio, Vol 8, Iss 6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bacteroides antagonism microbiota ubiquitin Microbiology QR1-502
spellingShingle	Bacteroides antagonism microbiota ubiquitin Microbiology QR1-502 Maria Chatzidaki-Livanis Michael J. Coyne Kevin G. Roelofs Rahul R. Gentyala Jarreth M. Caldwell Laurie E. Comstock Gut Symbiont <italic toggle="yes">Bacteroides fragilis</italic> Secretes a Eukaryotic-Like Ubiquitin Protein That Mediates Intraspecies Antagonism
description	ABSTRACT Human gut Bacteroides species produce different types of toxins that antagonize closely related members of the gut microbiota. Some are toxic effectors delivered by type VI secretion systems, and others are non-contact-dependent secreted antimicrobial proteins. Many strains of Bacteroides fragilis secrete antimicrobial molecules, but only one of these toxins has been described to date (Bacteroidales secreted antimicrobial protein 1 [BSAP-1]). In this study, we describe a novel secreted protein produced by B. fragilis strain 638R that mediated intraspecies antagonism. Using transposon mutagenesis and deletion mutation, we identified a gene encoding a eukaryotic-like ubiquitin protein (BfUbb) necessary for toxin activity against a subset of B. fragilis strains. The addition of ubb into a heterologous background strain conferred toxic activity on that strain. We found this gene to be one of the most highly expressed in the B. fragilis genome. The mature protein is 84% similar to human ubiquitin but has an N-terminal signal peptidase I (SpI) signal sequence and is secreted extracellularly. We found that the mature 76-amino-acid synthetic protein has very potent activity, confirming that BfUbb mediates the activity. Analyses of human gut metagenomic data sets revealed that ubb is present in 12% of the metagenomes that have evidence of B. fragilis. As 638R produces both BSAP-1 and BfUbb, we performed a comprehensive analysis of the toxin activity of BSAP-1 and BfUbb against a set of 40 B. fragilis strains, revealing that 75% of B. fragilis strains are targeted by one or the other of these two secreted proteins of strain 638R. IMPORTANCE We are just beginning to understand some of the important interactions that occur between microbes of the human gut microbiota that dictate the composition and abundance of its constituent members. The ability of one member to produce molecules that directly kill a coresident member has been shown among minor gut species and is just starting to be studied in the abundant Bacteroides species. Here, we show that some strains of Bacteroides fragilis have acquired a gene encoding a secreted eukaryotic-like ubiquitin protein with potent inhibitory activity against other B. fragilis stains. This is the first bacterially encoded ubiquitin-like molecule shown to function like a bacterial toxin. This molecule is an example of a gut symbiont acquiring and adapting a eukaryotic molecule likely to increase its competitiveness in the mammalian gut. Understanding antagonistic factors produced by abundant gut symbionts is an important prerequisite to properly engineer strains to colonize the gut for health benefits.
format	article
author	Maria Chatzidaki-Livanis Michael J. Coyne Kevin G. Roelofs Rahul R. Gentyala Jarreth M. Caldwell Laurie E. Comstock
author_facet	Maria Chatzidaki-Livanis Michael J. Coyne Kevin G. Roelofs Rahul R. Gentyala Jarreth M. Caldwell Laurie E. Comstock
author_sort	Maria Chatzidaki-Livanis
title	Gut Symbiont <italic toggle="yes">Bacteroides fragilis</italic> Secretes a Eukaryotic-Like Ubiquitin Protein That Mediates Intraspecies Antagonism
title_short	Gut Symbiont <italic toggle="yes">Bacteroides fragilis</italic> Secretes a Eukaryotic-Like Ubiquitin Protein That Mediates Intraspecies Antagonism
title_full	Gut Symbiont <italic toggle="yes">Bacteroides fragilis</italic> Secretes a Eukaryotic-Like Ubiquitin Protein That Mediates Intraspecies Antagonism
title_fullStr	Gut Symbiont <italic toggle="yes">Bacteroides fragilis</italic> Secretes a Eukaryotic-Like Ubiquitin Protein That Mediates Intraspecies Antagonism
title_full_unstemmed	Gut Symbiont <italic toggle="yes">Bacteroides fragilis</italic> Secretes a Eukaryotic-Like Ubiquitin Protein That Mediates Intraspecies Antagonism
title_sort	gut symbiont <italic toggle="yes">bacteroides fragilis</italic> secretes a eukaryotic-like ubiquitin protein that mediates intraspecies antagonism
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/b82fd22b110442cea1336cccb91552ed
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Gut Symbiont <italic toggle="yes">Bacteroides fragilis</italic> Secretes a Eukaryotic-Like Ubiquitin Protein That Mediates Intraspecies Antagonism

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