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Host-Microbe Interactions
Clostridium difficile
Anaerobic, gram-positive,
spore-forming, toxin
producing bacterium
Spores: environmentally
stable reservoir of the
organism
Can be detected in a
small fraction of the
healthy population
hastane.harran.edu.tr/enfek/gastroente.htm
Murine models of
C. difficile infection
Jhansi Leslie
Denovo
differentiation
iPSreprogramming
YamanakaFactors
HumanIntestinalOrganoid(HIO)
Mesenchyme+Epithelium
Simplegrowthconditions
(ENR)
biopsy
Enteroid
Epitheliumonly
Complexgrowthconditions
(ENRW,p38i,TGFi,etc)
Satoetal.,Gastroenterology,2011
Organoids as an alternative?
Replacement, Reduction, Refinement
Barrier permeability
assay
2h
10h
12h
14h
+EGTA
Control
+EGTA
Leslie et al. (2015) Infect Immun
2015 Jan;83(1):138-45
16h
18h
10h
12h
+EGTA
Control
+TcdB
+TcdA
+EGTA
14h
16h
18h
Control
TcdA
TcdB
Acknowledgments
NAMSED investigators: Jason Spence,
Sha Huang, David Hill, Stephanie Spohn,
Jhansi Leslie, Mary ORiordan, Christiane
Wobus, Shuichi Takayama, Robert
Britton, Eric Martens
The Young Lab: Jhansi Leslie, Angela
Hopkinson, Casey Theriot, Judy Opp,
Katherine Wozniak, Mark Koenigsknecht,
David Hill, Anna Seekatz
U19 AI090871
U19 AI116482