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Lab Meeting: new tract

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by

Elisa Margolis

on 23 July 2018

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Transcript of Lab Meeting: new tract

Lab Meeting: new focus
Clostridium difficile
-
Hypotheses for Infant Asymptomatic C. difficile
Lack toxin receptors
Plans
Daily infant stool samples to capture time of C. difficile colonization and use CCM to screen for members of microbiome which interact with C. difficile and toxin production
Preliminary Data
Would like to demonstrate that infant microbiome reduces toxin production of C. difficile
while deadly in particular hosts can also reside harmlessly in asymptomatic carriers
4 out of 5 infants will have C. difficile with no apparent symptoms
What are some reasons for a bacteria to be a pathogen in some hosts and commensal in other hosts?
some hosts higher pathogen load
(cholera exposure)
co-infections
(flu + s pneumo)
bacteria gets into
wrong location
(endocarditis)
differing immune responses
(vaccine, prior infection)
immune over-response
(TSS)
Not toxigenic/pathogenic strains of C difficile
Not high enough levels (no bloom)
Don't produce enough toxin & immune response is tempered
infant microbiome plays role in both
alternative
Hamster infant colonization model to look at immune response impact on pathogenesis
Historic Experiments
Toxin Gene Expression
gnotobiotic mice
C difficile Culture
Infant Stool
Toxin Production
(Toxin ELISA)
Toxin Gene
Expression
(qPCR of toxin genes)
Controls ?
toxin alters with temperature, nutrient availability
Preliminary Data
toxin discussion so far has been from host perspective- why does C. diff produce toxin?
increase transmission
competition with other bacteria
how would you test these hypotheses?
competition assays between toxigenic and non-toxigenic in sterile stool (long term survival)

toxins as bacteriocins- inhibition assays with adult microbiome flora
Raw feces, fecal water, constructed community?
need help figuring out experiments
Full transcript