Aspergillus fumigatus acetate utilisation impacts virulence traits and pathogenicity

<i>Aspergillus fumigatus</i> is a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection, <i>A. fumigatus</i> needs to use host carbon sources, such as acetate, present in the body fluids and peripheral tissues. However, utilisation of acetate as a carbon source by fungi in the context of infection has not been investigated. This work shows that acetate is metabolised via different pathways in <i>A. fumigatus</i> and that acetate utilisation is under the regulatory control of a transcription factor (TF), FacB. <i>A. fumigatus</i> acetate utilisation is subject to carbon catabolite repression (CCR), although this is only partially dependent on the TF and main regulator of CCR CreA. The available extracellular carbon source, in this case glucose and acetate, significantly affected <i>A. fumigatus</i> virulence traits such as secondary metabolite secretion and cell wall composition, with the latter having consequences for resistance to oxidative stress, to anti-fungal drugs and to human neutrophil-mediated killing. Furthermore, deletion of <i>facB</i> significantly impaired the <i>in vivo</i> virulence of <i>A. fumigatus</i> in both insect and mammalian models of invasive aspergillosis. This is the first report on acetate utilisation in <i>A. fumigatus</i> and this work further highlights the importance of available host-specific carbon sources in shaping fungal virulence traits and subsequent disease outcome, and a potential target for the development of anti-fungal strategies.