Live probiotic bacteria modulate the immune system to improve intestinal microbial balance and protect the host from foodborne pathogens and enteric diseases. The transient nature of probiotic bacteria in the gut prevents them from exerting their full health benefits. Persistence and stable colonization can happen when a probiotic bacterium finds a receptor on the host cells to cling on. The gastrointestinal mucosa represents the critical first site for the dynamic interaction of the enteric pathogens with the host. Therefore, averting this critical pathogen interaction step should help prevent extra-intestinal dissemination of pathogens and the consequent pathology. Listeria monocytogenes has been used as a model foodborne pathogen to study bioengineered probiotic approach. L. monocytogenes is an invasive human foodborne pathogen infecting primarily the immunocompromised host. The process by which it crosses the epithelial barrier is not fully understood. We show that Listeria adhesion protein (LAP; 94 kDa) induces intestinal epithelial barrier dysfunction to promote L. monocytogenes translocation. LAP binding to its cognate receptor, Hsp60 activates NF-κB signaling and facilitates myosin light-chain kinase (MLCK)-mediated opening of the epithelial barrier for bacterial translocation. A bioengineered Lactobacillus casei probiotic (BLP) expressing LAP helped probiotic interaction with Hsp60 forming a biofilm-like structure on the epithelial surface promoting anti-inflammatory and immunomodulatory responses through activation of Treg cells and improved gut barrier function. BLP protected mice and pregnant guinea pigs from listeriosis by competitive exclusion and immunomodulation, highlighting a novel approach in preventing infectious disease.

Receptor targeted bioengineered probiotic promote gut health and prevent enteric disease

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.