ChIP-seq and In Vivo Transcriptome Analyses of the SREBP SrbA Reveals a New Regulator of the Fungal Hypoxia Response and Virulence

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Despite improvements in diagnostics and antifungal drug treatments, mortality rates from invasive mold infections remain high. Defining the fungal adaptation and growth mechanisms at the infection site microenvironment is one research focus that is expected to improve treatment of established invasive fungal infections. The Aspergillus fumigatus transcription factor SrbA is a major regulator of the fungal response to hypoxia found at sites of invasive fungal growth in vivo. In this study, new insights into how SrbA mediates hypoxia adaptation and virulence were revealed through identification of direct transcriptional targets of SrbA under hypoxic conditions. A major novel finding from these studies is the identification of a critical role in fungal hypoxia adaptation and virulence of an SrbA target gene, srbB, which is also in the SREBP family. SrbB plays a major role in regulation of heme biosynthesis and carbohydrate metabolism early in the response to hypoxia. The discovery of SrbA-dependent regulation of srbB gene expression, and the target genes they regulate opens new avenues to understand how SREBPs and their target genes mediate adaptation to the in vivo infection site microenvironment and responses to current antifungal therapies.

Vyšlo v časopise: ChIP-seq and In Vivo Transcriptome Analyses of the SREBP SrbA Reveals a New Regulator of the Fungal Hypoxia Response and Virulence. PLoS Pathog 10(11): e32767. doi:10.1371/journal.ppat.1004487
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004487

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