Identification of an Aspergillus fumigatus protein which is involved in fungal growth in hypoxic conditions and in drug resistance

The incidence of potentially lethal infections caused by normally benign molds has increased tremendously over the last two decades. One disease in particular, invasive pulmonary aspergillosis (IPA), predominantly caused by the common mold Aspergillus fumigatus, has become the leading cause of death due to invasive infections. Currently, we have a limited understanding of how this opportunistic pathogen causes disease in immunocompromised patients.

A recent study by Willger et al has explored a mechanism required by this mold to cause disease, hypoxia (low oxygen) adaptation. The study states that hypoxia adaptation in Aspergillus fumigatus is mediated in part by a highly conserved transcription factor, SrbA, a protein in the sterol regulatory element binding protein family.
A mutant strain, not expressing SrbA was found to be unable to grow in hypoxic conditions, it also displayed increased susceptibility to the azole class of antifungal drugs – specifically it was highly susceptible to fluconazole and voriconazole, and was unable to cause disease in two distinct murine models of IPA.
Importantly, the authors report the discovery of a novel function of SrbA in molds related to maintenance of cell polarity. The finding that SrbA regulates resistance to the azole class of antifungal drugs presents an opportunity to uncover new mechanisms of antifungal drug resistance in A. fumigatus. Further details.