Organisme intervenant (ou équipe pour les séminaires internes)
Université Paris-Saclay - CNRS, UMR 9198 I2BC
Nom intervenant
Thomas Denecker
Functional networks of co-expressed genes to explore iron homeostasis processes in the pathogenic yeast

Joint woirk with Youfang ZHOU LI, Cécile FAIRHEAD, Karine BUDIN, Jean-Michel CAMADRO, Monique BOLOTIN-FUKUHARA, Adela ANGOULVANT and Gaëlle LELANDAIS

Infections due to Candida yeast species cause serious problems in aging populations and patients with compromised immunity. In this context, Candida glabrata has been reported as the second cause of candidiasis (1). Infections remain challenging to treat owing to delayed diagnosis, natural low susceptibility to azole antifungals and acquired resistance to echinocandins (2). During host infection, pathogens face abrupt physiological changes in their immediate environment. A major player is iron, as iron bioavailability is a key factor involved in the “nutritional immunity” host-defense mechanism (3). Remarkably, iron is a two-faced oligo-element for living organisms. On the one hand, iron is essential, as part of heme- and iron-sulfur cluster (ISC)-containing proteins involved in a variety of vital functions including oxygen transport, DNA synthesis, metabolic energy or cellular respiration and on the other hand, iron is toxic. Its excess triggers oxidative stress, lipid peroxidation and DNA damage that ultimately compromise cell viability and can promote programmed cell death. Iron homeostasis is therefore essential to allow pathogens to maintain a balance between iron utilization, storage, transport and uptake in the host environment.

The aim of the present work was to specifically study iron homeostasis in the pathogenic yeast C. glabrata. We performed transcriptomic experiments to monitor gene expression changes of C. glabrata to iron deficient and overload conditions, at 30°C and 37°C. The resulting dataset was analyzed to (i) clarify the potential effect of temperature on iron homeostasis, (ii) identify iron responsive genes, i.e genes significantly up- or down-regulated in at least one iron imbalanced situation and (iii) define a new set of genes, referred to as “iron homeostasis key genes” (iHKG). These genes are good candidates to be chief components of iron homeostasis. Our exploration of the datasets was facilitated by the inference of functional networks of co-expressed genes, which can be accessed through a web interface (https://thomasdenecker.github.io/iHKG/).

The philosophy of this work is to empower researchers by providing access to all transcriptomics data and by generating easily interpretable graphical outputs. This should facilitate deep exploration of genome-wide functional data in the pathogenic yeast C. glabrata to advance our global understanding of iron homeostasis.

1. Pfaller,M.A. and Diekema,D.J. (2007) Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem. Clin. Microbiol. Rev., 20, 133–163.Barbara Gastel and Robert A Day. How to write and publish a scientific paper. ABC-CLIO, 2016.
2. Pfaller,M.A., Castanheira,M., Lockhart,S.R., Ahlquist,A.M., Messer,S.A. and Jones,R.N. (2012) Frequency of Decreased Susceptibility and Resistance to Echinocandins among Fluconazole-Resistant Bloodstream Isolates of Candida glabrata. J. Clin. Microbiol., 50, 1199–1203.
3. Sutak,R., Lesuisse,E., Tachezy,J. and Richardson,D.R. (2008) Crusade for iron: iron uptake in unicellular eukaryotes and its significance for virulence. Trends Microbiol., 16, 261–268.

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