SREBP Coordinates Iron and Ergosterol Homeostasis to Mediate Triazole Drug and Hypoxia Responses in the Human Fungal Pathogen Aspergillus fumigatus

• DOI: 10.1371/journal.pgen.1002374
• Publication Date: 2011-12-03T04:48:44Z
• Authors: Michael Blatzer; Bridget M. Barker; Sven D. Willger; Nicola Beckmann; Sara J. Blosser; Elizabeth J. Cornish; Aurelien Mazurie; Nora Grahl; Hubertus Haas; Robert A. Cramer
• Keywords: Ergosterol; Antifungal drugs; Fungal protein

Sterol regulatory element binding proteins (SREBPs) are a class of basic helix-loop-helix transcription factors that regulate diverse cellular responses in eukaryotes. Adding to the recognized importance SREBPs human health, fungal pathogens Cryptococcus neoformans and Aspergillus fumigatus required for virulence susceptibility triazole antifungal drugs. To date, exact mechanism(s) behind role SREBP these observed phenotypes is not clear. Here, we report A. SREBP, SrbA, mediates regulation iron acquisition response hypoxia low conditions. further define SrbA's relation previously studied regulators metabolism, SreA HapX, series mutants were generated ΔsrbA background. These data suggest SrbA activated independently HapX limitation, but mRNA induction partially dependent on SrbA. Intriguingly, exogenous addition high or genetic deletion sreA background was able rescue growth, drug susceptibility, decrease ergosterol content ΔsrbA. Thus, conclude critical coordinating genes involved biosynthesis under conditions found at sites infections. results support SREBP–mediated virulence, they lay foundation exploration SREBP's homeostasis other