Aspergillus fumigatus AcuM regulates both iron acquisition and gluconeogenesis.

Liu H, Gravelat FN, Chiang LY, Chen D, Vanier G, Ejzykowicz DE, Ibrahim AS, Nierman WC, Sheppard DC, Filler SG.

Citation

Liu H, Gravelat FN, Chiang LY, Chen D, Vanier G, Ejzykowicz DE, Ibrahim AS, Nierman WC, Sheppard DC, Filler SG. (2010) Aspergillus fumigatus AcuM regulates both iron acquisition and gluconeogenesis. Molecular Microbiology 78(4):1038-1054.

Abstract

Relatively few transcription factors that govern the virulence of Aspergillus fumigatus are known. We constructed 11 A. fumigatus transcription factor mutants and screened them for altered virulence in Galleria mellonella larvae. We discovered that the zinc cluster transcription factor, AcuM, is essential for maximal virulence in this model, as well as in murine models of haematogenously disseminated and invasive pulmonary aspergillosis. Transcriptional profiling experiments suggested that AcuM suppresses sreA and induces hapX to stimulate expression of genes involved in both reductive iron assimilation and siderophore-mediated iron uptake. Consistent with these results, a ?acuM mutant had reduced iron incorporation, decreased extracellular siderophore production and impaired capacity to grow under iron-limited conditions. Interestingly, an Aspergillus nidulans?acuM mutant had normal extracellular siderophore production and growth under iron-limited conditions, indicating that AcuM does not govern iron acquisition in this organism. A. fumigatus AcuM also regulated genes involved in gluconeogenesis, and the ?acuM mutant had impaired growth on gluconeogenic carbon sources. Deletion of sreA in the ?acuM mutant restored iron uptake, extracellular siderophore production and virulence, but not the defect in gluconeogenesis. Thus, AcuM represses SreA and thereby induces iron acquisition, a process that is essential for the maximal virulence of A. fumigatus.