Arun Bhunia
Title:
Professor of Molecular Food Microbiology
PhD Granting Institution:
Purdue
Contact:
Email Address: bhunia@purdue.edu
Office Phone: 765-494-5443
Lab Website Link: https://ag.purdue.edu/foodsci/Pages/profile.aspx?strAlias=bhunia
Primary Training Group:
Microbiology, Immunnology, and Infectious Diseases
Research Areas:
Microbial pathogenesis, host immune response, and bioengineered probiotics approach in mitigating foodborne pathogen infection
Current Projects:
The crossing of the intestinal epithelial cell barrier is a crucial initial step for Listeria monocytogenes (Lm) pathogenesis. We reported that Lm can induce epithelial barrier dysfunction allowing bacterial paracellular translocation. This is largely attributed to the interaction of Listeria adhesion protein (LAP; 94 kDa), an alcohol acetaldehyde dehydrogenase enzyme with host cell receptor, Hsp60. The LAP-Hsp60 interaction activates canonical NF-κB signaling, facilitating myosin light-chain kinase (MLCK)-mediated opening of the epithelial barrier via the cellular junctional protein redistribution of claudin-1, occludin, and E-cadherin. Next, bioengineered Lactobacillus probiotics (BLP) strains expressing the LAP from a non-pathogenic Listeria (L. innocua) and Lm robustly colonized the intestine and protected mice from lethal Lm infection (92% survival). The BLP competitively excluded Lm by occupying the epithelial Hsp60 receptor and ameliorated the Lm-induced intestinal barrier dysfunction by limiting the loss of mucus-producing goblet cells, restricting epithelial apoptotic and proliferative cells, and blocking the NF-κB and MLCK-mediated redistribution of the epithelial junctional proteins. Additionally, the BLP increased intestinal immunomodulatory functions by recruiting FOXP3+T cells, CD11c+ dendritic cells and natural killer cells. Engineering a probiotic strain with an adhesion protein provides a novel strategy to prevent enteric pathogen colonization and infection.