In this section
@article{Mostyn:2026:10.64898/2026.08.05.742979,
author = {Mostyn, SN and Flores, K and Hedger, G and Nagaraj, H and Rouse, SL and Comstock, LE and Bubeck, D},
doi = {10.64898/2026.08.05.742979},
journal = {bioRxiv},
title = {Bacteroidales Secreted Antimicrobial Protein-1 receptor recognition is coupled to protease-activation to form bactericidal pores.},
url = {http://dx.doi.org/10.64898/2026.08.05.742979},
year = {2026}
}
TY - JOUR
AB - Bacteroidales secreted antimicrobial proteins (BSAPs) are diffusible MACPF-domain toxins that mediate intra-species antagonism in the gut microbiota. Here we define the mechanism of action of BSAP-1 from Bacteroides fragilis , showing how target specificity encoded within the N- and C-terminal domains is coordinated with pore-forming activity of the MACPF. We show that specificity of the toxin for its receptor is mediated by an extended interface comprised of the BSAP-1 C-terminal domain and residues on the receptor that differ from the orthologous protein of BSAP-1 producing strains. On the surface of susceptible cells, BSAP-1 undergoes proteolytic cleavage of an N-terminal regulatory domain, triggering its assembly into oligomeric pores. Cryo-electron microscopy of membrane-inserted BSAP-1 reveals a 13-subunit transmembrane β-barrel pore formed through canonical MACPF rearrangements. Comparative modelling supports a conserved oligomerization mechanism across the BSAP family despite diversification of receptor-binding domains that target either proteins or glycan receptors. Together, these findings establish BSAP-1 as a receptor-targeted, protease-activated antibacterial MACPF toxin and provide a framework for understanding how gut Bacteroidales spatially restrict toxin activation to shape strain-level competition.
AU - Mostyn,SN
AU - Flores,K
AU - Hedger,G
AU - Nagaraj,H
AU - Rouse,SL
AU - Comstock,LE
AU - Bubeck,D
DO - 10.64898/2026.08.05.742979
PY - 2026///
TI - Bacteroidales Secreted Antimicrobial Protein-1 receptor recognition is coupled to protease-activation to form bactericidal pores.
T2 - bioRxiv
UR - http://dx.doi.org/10.64898/2026.08.05.742979
UR - https://www.ncbi.nlm.nih.gov/pubmed/42620042
ER -