Chen C, Pande K, French SD, Tuch BB, Noble SM.. An iron homeostasis regulatory circuit with reciprocal roles in Candida albicans commensalism and pathogenesis. Cell Host Microbe 10: 118-135

Department of Medicine, Division of Infectious Diseases, University of California San Francisco, USA.
Cell host & microbe (Impact Factor: 12.19). 08/2011; 10(2):118-35. DOI: 10.1016/j.chom.2011.07.005
Source: PubMed

ABSTRACT The mammalian gastrointestinal tract and bloodstream are highly disparate biological niches that differ in concentrations of nutrients such as iron. However, some commensal-pathogenic microorganisms, such as the yeast Candida albicans, thrive in both environments. We report the evolution of a transcription circuit in C. albicans that controls iron uptake and determines its fitness in both niches. Our analysis of DNA-binding proteins that regulate iron uptake by this organism suggests the evolutionary intercalation of a transcriptional activator called Sef1 between two broadly conserved iron-responsive transcriptional repressors, Sfu1 and Hap43. Sef1 activates iron-uptake genes and promotes virulence in a mouse model of bloodstream infection, whereas Sfu1 represses iron-uptake genes and is dispensable for virulence but promotes gastrointestinal commensalism. Thus, C. albicans can alternate between genetic programs conferring resistance to iron depletion in the bloodstream versus iron toxicity in the gut, and this may represent a fundamental attribute of gastrointestinal commensal-pathogens.

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Available from: Kalyan Pande, Aug 25, 2015
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    • "During iron starvation, Sef1 affects expression of 223 genes positively or negatively, and the Sef1-activated genes are related to iron uptake including multicopper ferroxidase (fet3), iron permease (ftr1), ferric reductase (cfl1), siderophore transporter (sit1), heme iron uptake receptor (rbt5), and interestingly the CBC-binding factor (hap43; Chen et al., 2011). A role of the CBC-binding factors as principle regulators of iron-responsive genes has been studied in C. neoformans (CnHapX), A. fumigatus (AfHapX), and C. albicans (Hap43) (Jung et al., 2010; Schrettl et al., 2010a; Hsu et al., 2011). "
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    • "Genes are ranked based on the level of upregulation in the Wild Type 6 Fe condition. The x indicates genes previously identified to be similarly regulated by the HapX orthologs in A. fumigatus (Af; Schrettl et al., 2010), C. albicans (Ca; Chen et al., 2011), and S. pombe (Sp; Mercier et al., 2008) or by Cth1 and Cth2 in S. cerevisiae (Sc; Puig et al., 2008). a Genes whose differential expression was confirmed separately by real-time RT-PCR. "
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