Deciphering the inner workings of unique Bacteroides pore-forming toxins
(2024) Journée sécrétions — Location: Marseille, France (10.October.2024)
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- Authors
Lauber, Frédéric 
- et. al.
- Abstract
- The human gut microbiota is one of the densest and most complex microbial ecosystems on earth, harbouring hundreds of different species. This high microbial density and species diversity leads to fierce competition for nutrients and space, hence promoting bacterial antagonism. The Gram-negative Bacteroides are prominent long-term colonisers of the intestinal flora and represent on average 50% of all bacterial isolates within the human gut. They possess beneficial anti-inflammatory, immunomodulatory and metabolic properties hence playing a pivotal role in human health. To outmatch competitors, Bacteroides have evolved strategies to directly antagonize opponents through the production of antimicrobial molecules. Among these, the recently discovered Bacteroidales-secreted antimicrobial proteins (BSAPs) are of particular interest as they form a novel class of bacterial pore-forming toxins (PFTs). Indeed, co-culture experiments demonstrate that BSAP-producing strains kill sensitive cells in a BSAP-dependent manner by compromising cell envelope integrity. Interestingly, unlike other PFTs, BSAPs are highly specific to their respective targets, typically recognizing a single surface-exposed protein or O-antigen variant of a competitor. The underlying molecular mechanisms of this specificity remain so far cryptic. Here, we provide first biochemical insights into BSAP receptor recognition. Our findings indicate that the highly variable BSAP C-terminal domains are the sole factors responsible for receptor recognition and binding. In addition, we present preliminary structural data of a purified BSAP/receptor complex, allowing us to decipher this interaction. Additional bioinformatics analyses further expand these findings and indicate a clear CTD structure/target relationship. Taken together, our data provide the first biochemical evidence towards elucidating how these novel and poorly characterized PFTs operate, paving the way for future bioengineering projects.
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Citations
Lauber, F., & et al. (2024). Deciphering the inner workings of unique Bacteroides pore-forming toxins. Journée sécrétions, Marseille, France. https://hdl.handle.net/2078.5/215333