Receptor-targeted engineered probiotics mitigate lethal Listeria infection

Nat Commun. 2020 Dec 11;11(1):6344. doi: 10.1038/s41467-020-20200-5.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Bacterial Adhesion / genetics
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • CD11c Antigen
  • Cell Line
  • Chaperonin 60 / metabolism
  • Dendritic Cells
  • Disease Models, Animal
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Intestines / microbiology
  • Killer Cells, Natural
  • Lacticaseibacillus casei / genetics
  • Lacticaseibacillus casei / metabolism*
  • Listeria / genetics
  • Listeria monocytogenes / drug effects*
  • Listeria monocytogenes / genetics
  • Listeria monocytogenes / growth & development
  • Listeriosis / prevention & control*
  • Mice
  • Myosin-Light-Chain Kinase / metabolism
  • NF-kappa B / metabolism
  • Probiotics / metabolism*
  • Probiotics / pharmacology*
  • T-Lymphocytes

Substances

  • Bacterial Proteins
  • CD11c Antigen
  • Chaperonin 60
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • NF-kappa B
  • Myosin-Light-Chain Kinase

Supplementary concepts

  • Listeria innocua