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SUMMARY:Linking Pathogen Virulence\, the Microbiota and Disease - Professo
 r Gabriel Nunez\, Department of Pathology and Comprehensive Cancer Center\
 , University of Michigan
DTSTART:20130711T110000Z
DTEND:20130711T120000Z
UID:TALK46058@talks.cam.ac.uk
CONTACT:Suzy Blows
DESCRIPTION:The mechanisms that allow pathogens to colonize the intestine 
 and the indigenous microbiota to inhibit pathogen colonization remain uncl
 ear. We found that that germ-free animals are unable to eradicate Citrobac
 ter rodentium\, a model for human infections with attaching/effacing (A/E)
  bacteria. These Gram-negative bacteria are food- and waterborne non-invas
 ive pathogens which attach to and colonize the intestinal tract by inducin
 g characteristic A/E lesions on the intestinal epithelium\, leading to tra
 nsient enteritis or colitis in humans. The genome of A/E pathogens includi
 ng Enterohemorragic Escherichia coli (EHEC)\, enteropathogenic E. coli (EP
 EC) and C. rodentium harbor the locus of enterocyte effacement (LEE) that 
 is critical for bacterial colonization and the ability to cause pathology.
  We found that early in infection\, LEE virulence genes were expressed and
  required for pathogen growth in conventionally raised but not germ-free m
 ice.  LEE virulence gene expression was downregulated during the late phas
 e of infection\, which led to relocation of the pathogen to the intestinal
  lumen where it was out-competed by commensals. The ability of commensals 
 to out-compete C. rodentium was determined\, at least in part\, by the cap
 acity of the pathogen and commensals to grow on structurally similar carbo
 hydrates. Moreover\, we found that dietary carbohydrates can influence the
  ability of members of the gut microbiota to out-compete the pathogen in t
 he intestine. Our studies indicate the members of the microbiota use metab
 olic pathways to out-compete pathogens. Furthermore\, intestinal pathogens
  have developed strategies to avoid competition with commensals based on t
 he expression of virulence factors during the early phase of the infection
 . \n\nReference:\n\nKamada N. Kim YG\, Sham HP\, Vallance BA\, Puente JL\,
  Martens EC\, Núñez G.  Regulated virulence controls the ability of a pa
 thogen to compete with the gut microbiota. Science 336:1325-1329\, 2012. 
LOCATION:Lecture Theatre 1\, Department of Veterinary Medicine
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