A Common Pathway for Activation of Host-Targeting and Bacteria-Targeting Toxins in Human Intestinal Bacteria

ABSTRACT Human gut microbes exhibit a spectrum of cooperative and antagonistic interactions with their host and also with other microbes. The major Bacteroides host-targeting virulence factor, Bacteroides fragilis toxin (BFT), is produced as an inactive protoxin by enterotoxigenic B. fragilis strain...

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Autores principales:	Yiqiao Bao, Andrew A. Verdegaal, Brent W. Anderson, Natasha A. Barry, Jing He, Xiang Gao, Andrew L. Goodman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	bacteriocin Bacteroides interbacterial interaction microbiome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9730b221a4864a5dbd80420b95bf24b1
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spelling	oai:doaj.org-article:9730b221a4864a5dbd80420b95bf24b12021-11-10T18:37:50ZA Common Pathway for Activation of Host-Targeting and Bacteria-Targeting Toxins in Human Intestinal Bacteria10.1128/mBio.00656-212150-7511https://doaj.org/article/9730b221a4864a5dbd80420b95bf24b12021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00656-21https://doaj.org/toc/2150-7511ABSTRACT Human gut microbes exhibit a spectrum of cooperative and antagonistic interactions with their host and also with other microbes. The major Bacteroides host-targeting virulence factor, Bacteroides fragilis toxin (BFT), is produced as an inactive protoxin by enterotoxigenic B. fragilis strains. BFT is processed by the conserved bacterial cysteine protease fragipain (Fpn), which is also encoded in B. fragilis strains that lack BFT. In this report, we identify a secreted antibacterial protein (fragipain-activated bacteriocin 1 [Fab1]) and its cognate immunity protein (resistance to fragipain-activated bacteriocin 1 [RFab1]) in enterotoxigenic and nontoxigenic strains of B. fragilis. Although BFT and Fab1 share no sequence identity, Fpn also activates the Fab1 protoxin, resulting in its secretion and antibacterial activity. These findings highlight commonalities between host- and bacterium-targeting toxins in intestinal bacteria and suggest that antibacterial antagonism may promote the conservation of pathways that activate host-targeting virulence factors. IMPORTANCE The human intestine harbors a highly complex microbial community; interpersonal variation in this community can impact pathogen susceptibility, metabolism, and other aspects of health. Here, we identified and characterized a commensal-targeting antibacterial protein encoded in the gut microbiome. Notably, a shared pathway activates this antibacterial toxin and a host-targeting toxin. These findings highlight unexpected commonalities between host- and bacterium-targeting toxins in intestinal bacteria.Yiqiao BaoAndrew A. VerdegaalBrent W. AndersonNatasha A. BarryJing HeXiang GaoAndrew L. GoodmanAmerican Society for MicrobiologyarticlebacteriocinBacteroidesinterbacterial interactionmicrobiomeMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bacteriocin Bacteroides interbacterial interaction microbiome Microbiology QR1-502
spellingShingle	bacteriocin Bacteroides interbacterial interaction microbiome Microbiology QR1-502 Yiqiao Bao Andrew A. Verdegaal Brent W. Anderson Natasha A. Barry Jing He Xiang Gao Andrew L. Goodman A Common Pathway for Activation of Host-Targeting and Bacteria-Targeting Toxins in Human Intestinal Bacteria
description	ABSTRACT Human gut microbes exhibit a spectrum of cooperative and antagonistic interactions with their host and also with other microbes. The major Bacteroides host-targeting virulence factor, Bacteroides fragilis toxin (BFT), is produced as an inactive protoxin by enterotoxigenic B. fragilis strains. BFT is processed by the conserved bacterial cysteine protease fragipain (Fpn), which is also encoded in B. fragilis strains that lack BFT. In this report, we identify a secreted antibacterial protein (fragipain-activated bacteriocin 1 [Fab1]) and its cognate immunity protein (resistance to fragipain-activated bacteriocin 1 [RFab1]) in enterotoxigenic and nontoxigenic strains of B. fragilis. Although BFT and Fab1 share no sequence identity, Fpn also activates the Fab1 protoxin, resulting in its secretion and antibacterial activity. These findings highlight commonalities between host- and bacterium-targeting toxins in intestinal bacteria and suggest that antibacterial antagonism may promote the conservation of pathways that activate host-targeting virulence factors. IMPORTANCE The human intestine harbors a highly complex microbial community; interpersonal variation in this community can impact pathogen susceptibility, metabolism, and other aspects of health. Here, we identified and characterized a commensal-targeting antibacterial protein encoded in the gut microbiome. Notably, a shared pathway activates this antibacterial toxin and a host-targeting toxin. These findings highlight unexpected commonalities between host- and bacterium-targeting toxins in intestinal bacteria.
format	article
author	Yiqiao Bao Andrew A. Verdegaal Brent W. Anderson Natasha A. Barry Jing He Xiang Gao Andrew L. Goodman
author_facet	Yiqiao Bao Andrew A. Verdegaal Brent W. Anderson Natasha A. Barry Jing He Xiang Gao Andrew L. Goodman
author_sort	Yiqiao Bao
title	A Common Pathway for Activation of Host-Targeting and Bacteria-Targeting Toxins in Human Intestinal Bacteria
title_short	A Common Pathway for Activation of Host-Targeting and Bacteria-Targeting Toxins in Human Intestinal Bacteria
title_full	A Common Pathway for Activation of Host-Targeting and Bacteria-Targeting Toxins in Human Intestinal Bacteria
title_fullStr	A Common Pathway for Activation of Host-Targeting and Bacteria-Targeting Toxins in Human Intestinal Bacteria
title_full_unstemmed	A Common Pathway for Activation of Host-Targeting and Bacteria-Targeting Toxins in Human Intestinal Bacteria
title_sort	common pathway for activation of host-targeting and bacteria-targeting toxins in human intestinal bacteria
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/9730b221a4864a5dbd80420b95bf24b1
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A Common Pathway for Activation of Host-Targeting and Bacteria-Targeting Toxins in Human Intestinal Bacteria

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