Candida Infection Biology – fungal armoury, battlefields ... - FINSysB

Interaction of a Candida glabrata transcription factor
knock-out library with the Drosophila melanogaster innate
immune system
Jane Usher 3 , Ilias Kounatidis 1 , Biao Ma 2 , Petros Ligoxygakis 1 &
Ken Haynes 3
University of Oxford 1 , Imperial College London 2 , University of Exeter 3
At least in part Candida species are thought to invade following initial
gastrointestinal colonisation. The mechanisms underpinning this translocation
depend on many factors including host intestinal flora, mucosal damage and
deficient host immunity. In addition fungal attributes eg the ability to acquire
nutrients and to adapt to host environmental insults are essential to disease
initiation and progression.
To analyse this interaction on a holistic level we have created a library of Candida
glabrata mutants and developed a Drosophila melanogaster model of
gastrointestinal candidosis. A library of ~200 bar coded mutant strains, each lacking
a specific DNA binding protein, was constructed in a derivative of C. glabrata ATCC
2001. Each of these was screened in a D. melanogaster larval GI infection model,
in which third instar larvae, containing a Drs-GFP allele, were fed with C. glabrata
infected food. Drosomycin (Drs) is activated in the larval fat body in response to
wild-type C. glabrata colonization. Of the 200 knock-out mutants 12 failed to
activate Drs-GFP indicating reduced activation of host innate immunity. We are
currently investigating the basis of this reduced activation.
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