Hydrocortisone-enhanced growth of Aspergillus spp.: implications for pathogenesis

Aspergillus fumigatus and Aspergillus flavus are the most common cause of invasive mould infections worldwide and carry a high mortality. Corticosteroid therapy and Cushing's disease are associated with an increase in invasive aspergillosis. Corticosteroids impair immune function in mammals and, specifically, the conidicidal activity of human macrophages, which was thought to be sufficient explanation for this increased risk. However, we have found a 30-40% increase in growth rate of A. fumigatus and A. flavus exposed to pharmacological doses of hydrocortisone (a human glucocorticoid), suggesting an alternative or additional mechanism for the association. No significant effect was observed with other human steroids such as testosterone, oestradiol or progesterone, though a smaller (21%) but significant growth rate increase was obtained with the fungal sterol ergosterol. The presence of a ligand/receptor system is therefore possible in pathogenic Aspergillus spp. Although corticosterone-binding proteins have been identified in some yeast species, a demonstrable physiological effect has been lacking. Interruption of the putative ligand/receptor interaction could have a major effect on the growth and pathogenicity of A. fumigatus, providing opportunities for the development of alternative therapeutic strategies to those currently available.