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ARS Home » Northeast Area » Wyndmoor, Pennsylvania » Eastern Regional Research Center » Molecular Characterization of Foodborne Pathogens Research » Research » Publications at this Location » Publication #386095

Research Project: Development of Innovative Technologies and Strategies to Mitigate Biological, Chemical, Physical, and Environmental Threats to Food Safety

Location: Molecular Characterization of Foodborne Pathogens Research

Title: Receptor-targeted engineered probiotics mitigate lethal Listeria infection

Author
item DROLIA, RISHI - Purdue University
item AMALARADJOU, MARY - Purdue University
item RYAN, VALERIE - Purdue University
item TENGURIA, SHIVENDRA - Purdue University
item LIU, DONGQI - Purdue University
item BAI, XINGJIAN - Purdue University
item XU, LUPING - Purdue University
item SINGH, ATUL - Purdue University
item COX, ABIGAIL - Purdue University
item BERNAL-CRESPO, VICTOR - Purdue University
item SCHABER, JAMES - Purdue University
item APPLEGATE, BRUCE - Purdue University
item VEMULAPALLI, RAMESH - Purdue University
item BHUNIA, ARUN - Purdue University

Submitted to: Nature Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2020
Publication Date: 12/11/2020
Citation: Drolia, R., Amalaradjou, M., Ryan, V., Tenguria, S., Liu, D., Bai, X., Xu, L., Singh, A.K., Cox, A.D., Bernal-Crespo, V., Schaber, J.A., Applegate, B.M., Vemulapalli, R., Bhunia, A.K. 2020. Receptor-targeted engineered probiotics mitigate lethal Listeria infection. Nature Communications. doi.org/10.1038/s41467-020-20200-5. https://doi.org/10.1038/s41467-020-20200-5.
DOI: https://doi.org/10.1038/s41467-020-20200-5

Interpretive Summary: Probiotic bacteria reduce the intestinal colonization of pathogens. Yet, their use in preventing fatal infections caused by foodborne Listeria monocytogenes (Lm) is inconsistent. In this study a non-pathogenic bacterium, Lactobacillus casei was engineered to express the Listeria adhesion protein (LAP). These bioengineered Lactobacillus probiotics (BLP) express the Listeria adhesion protein (LAP) on the surface of Lactobacillus casei. When mice were orally dosed with BLP, the strains colonized the intestine, reduced Lm mucosal colonization and systemic dissemination, and protected mice from lethal infection. Engineering a probiotic strain with an adhesion protein from a non-pathogenic bacterium provides a new paradigm to exclude pathogens and amplify their inherent health benefits.

Technical Abstract: Probiotic bacteria reduce the intestinal colonization of pathogens. Yet, their use in preventing fatal infection caused by foodborne Listeria monocytogenes (Lm), is inconsistent. Here, we bioengineered Lactobacillus probiotics (BLP) to express the Listeria adhesion protein (LAP) from a non-pathogenic Listeria (L. innocua) and a pathogenic Listeria (Lm) on the surface of Lactobacillus casei. The BLP strains colonize the intestine, reduce Lm mucosal colonization and systemic dissemination, and protect mice from lethal infection. The BLP competitively excludes Lm by occupying the surface presented LAP receptor, heat shock protein 60 and ameliorates the Lm-induced intestinal barrier dysfunction by blocking the nuclear factor-'B and myosin light chain kinase-mediated redistribution of the major epithelial junctional proteins. Additionally, the BLP increases intestinal immunomodulatory functions by recruiting FOXP3+T cells, CD11c+ dendritic cells and natural killer cells. Engineering a probiotic strain with an adhesion protein from a non-pathogenic bacterium provides a new paradigm to exclude pathogens and amplify their inherent health benefits.