Odoribacter splanchnicusmitigatesSalmonella-induced gut inflammation and its associated pathogenesis via its secreted bacteriocin

Abstract

ABSTRACTFoodborne pathogens continue to be a leading concern of health hazards worldwide claiming the lives of millions. The emergence of drug-resistant strains poses a great threat to global world health management. Therefore, designing novel therapeutic strategies aiming to overcome pathogen burden is of utmost importance. Here, we identified the crucial role of a gut-commensal species,Odoribacter splanchnicusin mitigatingSalmonellapathogenesis in mice by inhibiting gut vascular barrier disruption, acute inflammatory infection signs,in vivobiofilm formation and by preserving tight junction protein functions upon pre-colonization. Further, ourin vitrostudies revealed that not only liveO. splanchnicus(OS) but also its culture supernatant inhibitSalmonellabiofilm formation, intracellular proliferation in human intestinal cells, and its virulence gene expression. In addition, OS’s inhibitory effect onSalmonellais specific asEnterococcus faecalisfails to exert an inhibitory effect onSalmonella. Further, our results depicted that the specific protective role of OS acts over a broad spectrum as it confers protection against flagellated Gram-positive,Listeria monocytogenesand Gram-negative,SalmonellaTyphimurium foodborne pathogens, as opposed to non-flagellatedShigella flexneri. Moreover, OS conferred protection even after its administration to mice post-establishment of infection highlighting its therapeutic potential. Using several biochemical and proteomics approaches, we characterized the key active molecule secreted by OS to limit intracellularSalmonellaandListeriareplication in human intestinal epithelial cells by regulating key virulence effectors and flagella. Collectively, our study highlights the broad-spectrum protective role of OS in mitigatingSalmonellaandListeriapathogenesis and implicates its therapeutic potential.