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 Lactobacillusprobiotics (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.
Highlights
Probiotic bacteria reduce the intestinal colonization of pathogens
The general preventive precautionary guidelines outlined by the Centers for Disease Control and Prevention (CDC) are thorough cooking of meat, safe food handling practices, and avoidance of the Food and Drug Administration (FDA) designated high-risk foods, such as frankfurters, soft cheeses made with unpasteurized milk, paté, smoked fish, and cantaloupe
We further demonstrate that the bioengineered Lactobacillus probiotics (BLP) occupies the host receptor, Hsp[60], and prevents Listeria monocytogenes (Lm) translocation and infection by competitive exclusion, the Lm-induced nuclear factor-κB (NF-κB) and myosin light-chain kinase (MLCK) activation, myosin light chain (MLC) phosphorylation, and subsequent redistribution of the major epithelial junctional proteins to preserve intestinal epithelial barrier integrity
Summary
Probiotic bacteria reduce the intestinal colonization of pathogens Their use in preventing fatal infection caused by foodborne Listeria monocytogenes (Lm), is inconsistent. The major limitations of probiotics for prophylactic or therapeutic use are their poor ability to colonize the intestine and exhibit a weaker capacity to compete with pathogens and exert immunomodulatory actions[7,14,15]. To overcome these limitations of traditional probiotics, next-generation bioengineered probiotic strains can be designed to incorporate desirable traits[16,17,18]. Cost-effective strategies that prevent Lm infection and the progression of the disease are urgently needed
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