REGULATION OF FUNGAL EXTRACELLULAR PROTEASES AND THEIR ROLE IN MAMMALIAN PATHOGENESIS

Fungal infection in the immunocompromised host is a problem of increasing importance. The virulence determinants of Aspergillus fumigatus, the major agent of invasive aspergillosis, and of Candida albicans, causing candidiasis, are not well characterized. For both pathogens, the involvement of extracellular proteases in pathogenesis is discussed. The use of gene disruption techniques to inactivate the A. fumigatus alkaline protease and metalloprotease genes has led to the firm conclusion that neither of these enzymes has a significant role in virulence. The diploid nature of C. albicans (necessitating sequential inactivation of both alleles for gene disruption studies) and the presence of a multigene family encoding secreted aspartyl proteases has hampered progress in understanding the role of proteases in virulence. We discuss the involvement of wide-domain regulators in the control of protease production and give an example of how one of these regulators (encoded by the are A gene) has been used in virulence studies.