Receptor-targeted engineered probiotics mitigate lethal Listeria infection

Rishi Drolia, Mary Anne Roshni Amalaradjou, Valerie Ryan, Shivendra Tenguria, Dongqi Liu, Xingjian Bai, Luping Xu, Atul K. Singh, Abigail D. Cox, Victor Bernal-Crespo, James A. Schaber, Bruce M. Applegate, Ramesh Vemulapalli and Arun K. Bhunia ()
Additional contact information
Rishi Drolia: Purdue University
Mary Anne Roshni Amalaradjou: Purdue University
Valerie Ryan: Purdue University
Shivendra Tenguria: Purdue University
Dongqi Liu: Purdue University
Xingjian Bai: Purdue University
Luping Xu: Purdue University
Atul K. Singh: Purdue University
Abigail D. Cox: Purdue University
Victor Bernal-Crespo: Purdue University
James A. Schaber: Purdue University
Bruce M. Applegate: Purdue University
Ramesh Vemulapalli: Purdue University
Arun K. Bhunia: Purdue University

Nature Communications, 2020, vol. 11, issue 1, 1-23

Abstract: 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-κB 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-20200-5

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DOI: 10.1038/s41467-020-20200-5

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