title: Caenorhabditis elegans susceptibility to gut Enterococcus faecalis infection is associated with fat metabolism and epithelial junction integrity.
abstract: BACKGROUND
  Gut bacteria-host interactions have been implicated in the pathogenesis of numerous human diseases, but few mechanisms have been described. The genetically tractable nematode worm Caenorhabditis elegans can be infected with pathogenic bacteria, such as the human gut commensal Enterococcus faecalis, via feeding, making it a good model for studying these interactions.
  
  
  RESULTS
  An RNAi screen of 17 worm candidate genes revealed that knockdown of the transcription factor nhr-49, a master regulator of fat metabolism, shortens worm lifespan upon infection with E. faecalis (and other potentially pathogenic bacteria) compared to Escherichia coli. The functional similarity of nhr-49 to the mammalian peroxisome proliferator-activated receptors (PPARs) suggests that this is mediated through a link between fatty acid metabolism and innate immunity. In addition, knockdown of either dlg-1 or ajm-1, which encode physically interacting proteins in the C. elegans epithelial junction, also reduces worm lifespan upon E. faecalis challenge, demonstrating the importance of the intestinal epithelium as an immune barrier.
  
  
  CONCLUSIONS
  The protective roles identified for nhr-49, dlg-1, and ajm-1 suggest mechanistic interactions between the gut microbiota, host fatty acid metabolism, innate immunity, and epithelial junction integrity that are remarkably similar to those implicated in human metabolic and inflammatory diseases.
authors.affiliation: Infectious Diseases, Genome Institute of Singapore, 60 Biopolis Street, #02-01 Genome, Singapore, 138672, Singapore. shuzhens@gis.a-star.edu.sg.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Sim
authors.affiliation: Infectious Diseases, Genome Institute of Singapore, 60 Biopolis Street, #02-01 Genome, Singapore, 138672, Singapore.|Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D013293:Enterococcus faecalis / Q000502:physiology*; D005223:Fats / Q000378:metabolism*; D005260:Female; D000069196:Gastrointestinal Microbiome; D016908:Gram-Positive Bacterial Infections / Q000378:metabolism / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology*; D008297:Male
chemical_list: D029742:Caenorhabditis elegans Proteins; D005223:Fats