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

Bao, Yiqiao; Verdegaal, Andrew A; Anderson, Brent; Barry, Natasha A.; He, Jing; Gao, Xiang; Goodman, Andrew L.

doi:10.1128/mbio.00656-21

Cited by 5 publications

(5 citation statements)

References 43 publications

(86 reference statements)

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“…vulgatus and Ph. dorei; bacteroidetocin A and B, which are widely distributed among gut Bacteroidaceae; 29 and Fab1 62 and BfUbb, 69 which are restricted to B. fragilis. As expected, a subset of strains of the expected species contains the genes encoding each of these toxins with the exception of BfUbb, which was not encoded in any of the 7 B. fragilis genomes in our collection, consistent with a previous reported prevalence of 14% among sequenced B. fragilis strains.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species and strain level diversity and evolution

Zhang,

Cole,

Coyne

et al. 2024

Preprint

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Species of the Bacteroidales order are among the most abundant and stable bacterial members of the human gut microbiome with diverse impacts on human health. While Bacteroidales strains and species are genomically and functionally diverse, order-wide comparative analyses are lacking. We cultured and sequenced the genomes of 408 Bacteroidales isolates from healthy human donors representing nine genera and 35 species and performed comparative genomic, gene-specific, mobile gene, and metabolomic analyses. Families, genera, and species could be grouped based on many distinctive features. However, we also show extensive DNA transfer between diverse families, allowing for shared traits and strain evolution. Inter- and intra-specific diversity is also apparent in the metabolomic profiling studies. This highly characterized and diverse Bacteroidales culture collection with strain-resolved genomic and metabolomic analyses can serve as a resource to facilitate informed selection of strains for microbiome reconstitution.

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Section: Resultsmentioning

confidence: 99%

Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species and strain level diversity and evolution

Zhang,

Cole,

Coyne

et al. 2024

Preprint

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“…The toxin exhibits unusual features, including the necessity for two proteolytic cleavage events for receptor binding and activity. As far as we know, the dual cleavage required to activate BcpT has not been observed for other characterized proteolytically activated toxin, which require only a single cleavage for activation (e.g., anthrax toxin, diphtheria toxin 29 Bft, bacteroidetocins, Fab1 6 , class IIa bacteriocins, etc) and is the first antimicrobial toxin produced by the gut Bacteroidales shown to bind the Lipid A-core glycan. It is yet unknown if BcpT is glycosylated and if so, how such glycosylation would affect its processing, activity, and stability.…”

Section: Discussionmentioning

confidence: 99%

“…Bacteroidales species antagonize by both contact-dependent and contact-independent mechanisms. Contact-independent antagonism has been shown to be mediated by antimicrobial toxins that fall into four distinct families: the BSAP (Bacteroidales Secreted Antimicrobial Protein) toxins 1 – 4 , the peptide bacteroidetocins 5 , the Fab1 toxin 6 , and a ubiquitin-like toxin (BfUbb) 7 . The BSAPs are produced by diverse members of Bacteroidetes and contain membrane attack complex/perforin (MACPF) domains and typically kill strains of the same or similar species, likely by pore formation.…”

Section: Introductionmentioning

confidence: 99%

A proteolytically activated antimicrobial toxin encoded on a mobile plasmid of Bacteroidales induces a protective response

et al. 2022

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Phocaeicola vulgatus is one of the most abundant and ubiquitous bacterial species of the human gut microbiota, yet a comprehensive analysis of antibacterial toxin production by members of this species has not been reported. Here, we identify and characterize a previously undescribed antibacterial protein. This toxin, designated BcpT, is encoded on a small mobile plasmid that is largely confined to strains of the closely related species Phocaeicola vulgatus and Phocaeicola dorei. BcpT is unusual in that it requires cleavage at two distinct sites for activation, and we identify bacterial proteases that perform this activation. We further identify BcpT’s receptor as the Lipid A-core glycan, allowing BcpT to target species of other Bacteroidales families. Exposure of cells to BcpT induces a response involving an unusual sigma/anti-sigma factor pair that is likely triggered by cell envelope stress, resulting in the expression of genes that partially protect cells from multiple antimicrobial toxins.

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“…Another toxin with antibacterial activity, Fab1, is produced by enterotoxigenic and nontoxic B. fragilis strains (24). Whereas these mechanisms demonstrate the capability for interactions, generalizing these results and applying this knowledge to communities of naturally co-existing strains and species remains a challenge.…”

Section: Introductionmentioning

confidence: 99%

“…B. vulgatus itself was shown in another study to inhibit the growth of other Bacteroides species by producing bacteroidetocin A, a diffusible peptide belonging to a large family of bacterial toxins (23). Another toxin with antibacterial activity, Fab1, is produced by enterotoxigenic and nontoxic B. fragilis strains (24). Whereas these mechanisms demonstrate the capability for interactions, generalizing these results and applying this knowledge to communities of naturally co-existing strains and species remains a challenge.…”

Section: Introductionmentioning

confidence: 99%

Closely relatedBacteroidesof the murine intestinal microbiota affect each other’s growth positively or negatively

Fokt

Šakalytė

Unni

et al. 2023

Preprint

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The mammalian intestine is a unique ecosystem for thousands of bacterial species and strains. How naturally coexisting bacteria of the microbiota interact with each other is not yet fully understood. Here, we isolated formerly coexisting, closely related strains of the genusBacteroidesfrom the intestines of healthy, wild-derived mice. The effect of one strain on another strain’s growth was tested in 169 pairsin vitro. We find a vast diversity of growth promoting and growth inhibiting activities. A strong positive effect was observed between two strains with differing metabolisms. Growth inhibition among a subset of strains was associated with the known bacterial toxin bacteroidetocin B. Across all strains, we observed growth promotion more often than growth inhibition. The effects were independent of two strains belonging to the same or different species. In some cases, one species differed in its effect on another according to host origin. These findings on obligate host-associated bacteria demonstrate that closely related and naturally coexisting strains have the potential to affect each other’s growth positively or negatively. These results have implications for our basic understanding of host-associated microbes and the design of synthetic microbial communities.

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

Cited by 5 publications

References 43 publications

Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species and strain level diversity and evolution

Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species and strain level diversity and evolution

A proteolytically activated antimicrobial toxin encoded on a mobile plasmid of Bacteroidales induces a protective response

Closely relatedBacteroidesof the murine intestinal microbiota affect each other’s growth positively or negatively

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