Cellular membrane protein MipA from E.coli Nissle 1917 protects against Salmonella infection.

Abstract

Intestinal microbiota resists pathogenic bacterial infections through colonization resistance, largely attributed to direct microbial competition. However, whether commensals can provide colonization resistance by remodeling the host epithelial niche remains underexplored. Here, by combining in vivo mouse models and a gut-on-chip model, this study demonstrates that the resistance of commensal Escherichia coli Nissle 1917 (EcN) against Salmonella Typhimurium (STm) infection is strictly dependent on EcN precolonization. Mechanistically, the EcN outer membrane protein MipA was identified as a key factor that induces the upregulation of integrin-linked kinase (ILK), thereby reinforcing tight junction integrity and restricting Salmonella infection. Engineering a nonprotective strain to express MipA was sufficient to confer resistance against Salmonella infection. This work reveals an epithelial defense mechanism triggered by a specific probiotic protein, with implications for developing preventive strategies against enteric infections.