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Exploiting a host-commensal interaction to promote intestinal barrier function and enteric pathogen tolerance

Virginia A Pedicord1,2, Ainsley A K Lockhart1, Kavita J Rangan2

  • 1Laboratory of Mucosal Immunology, The Rockefeller University, New York, NY, USA.

Science Immunology
|June 6, 2017
PubMed

Insights

A specific bacterium, Enterococcus faecium, enhances gut barrier defenses against pathogens like Salmonella Typhimurium and Clostridium difficile. Its unique enzyme, SagA, can be used to boost resistance to enteric infections.

Area of Science:

  • Microbiology
  • Immunology
  • Gastroenterology

Background:

  • Commensal gut bacteria play a role in preventing infections.
  • Understanding the mechanisms of pathogen resistance mediated by specific commensal species is crucial for therapeutic development.

Purpose of the Study:

  • To investigate how the human commensal Enterococcus faecium protects against enteric infections.
  • To identify the specific bacterial factors and host mechanisms involved in this protection.

Main Methods:

  • Colonization of mice with Enterococcus faecium.
  • Analysis of host intestinal epithelial defense programs.
  • Identification of bacterial factors using genetic approaches.
  • Ectopic expression of bacterial factors in other bacteria.

Main Results:

  • Enterococcus faecium colonization enhances host intestinal epithelial defense against Salmonella Typhimurium.
  • Protection is mediated by the peptidoglycan hydrolase SagA and requires host pattern recognition receptors and antimicrobial peptides.
  • Ectopic expression of SagA confers resistance against Salmonella Typhimurium and Clostridium difficile.

Conclusions:

  • Enterococcus faecium enhances host barrier function to limit enteric pathogen pathogenesis.
  • The bacterial enzyme SagA is a key factor in mediating this protection.
  • Specific factors from commensal bacteria can be harnessed to improve host defense and combat distinct enteric infections.

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