Aspergillus fumigatus acetate utilisation impacts virulence traits and pathogenicity

Aspergillus
fumigatus is a major opportunistic
fungal pathogen of immunocompromised and immunocompetent hosts. To successfully
establish an infection, A. fumigatus
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 A. fumigatus and that acetate utilisation is under the regulatory
control of a transcription factor (TF), FacB. A. fumigatus 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 A.
fumigatus 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 facB
significantly impaired the in vivo
virulence of A. fumigatus in both
insect and mammalian models of invasive aspergillosis. This is the first report
on acetate utilisation in A. fumigatus
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.