Brucella Abortus Outer Membrane Protein Modulates Host Immunity Via B-Cell Receptor-Associated Protein Publisher



Khonsari Y N ; Habibi R ; Alami F ; Mustafa R M ; Varkiani M M ; Banimahdidehkordi A ; Fekri M ; Asl H B ; Moosavi M ; Heidari Soureshjani E
Source: AMB Express Published:2026

Abstract

Brucella outer membrane protein 10 (OMP10) plays a critical role in host–pathogen interactions, yet its molecular mechanisms in modulating inflammatory and apoptotic pathways remain unclear. Here, we combined in vivo transcriptional profiling with computational analyses to investigate OMP10 function. Oral delivery of OMP10-expressing Lactococcus lactis in mice induced significant upregulation of BCAP31, CASP8, and IL1B, indicating engagement of ER stress, apoptotic, and NF-κB–mediated inflammatory responses. Protein–protein interaction network analysis across STRING confidence thresholds (0.4, 0.7, 0.9) highlighted CASP8 and IL1B as central hubs, with BCAP31 and PACS2 as key intermediates. Sequence-based docking and molecular dynamics simulations identified stable, energetically favorable interactions between OMP10 and BCAP31, PACS2, and TNFSF10, consistent with modulation of ER–MAM signaling and caspase-8 priming. Functional enrichment linked these interactions to unfolded protein response, CASP8 activation, and IL-1β production. Collectively, these results reveal OMP10 as a multifunctional Brucella effector that orchestrates ER stress–inflammation–apoptosis crosstalk and suggest that targeting the OMP10–BCAP31 axis could inform novel therapeutic or vaccine strategies against brucellosis. © The Author(s) 2026.