The role of secretory and structure-associated proteinases of Aspergillus fumigatus in the pathogenesis of invasive aspergillosis

Abstract

In the course of invasive aspergillosis, Aspergillus fumigatus is capable of penetrating any tissue of the host. Secretory proteinases of the fungus might facilitate the hyphae to grow through fibrillar proteins like elastin and collagen. However; using systemic infection models, no significantly reduced virulence could be shown with fungal mutants deficient for all known secretory proteinases. Thus, secretory proteinases might he of minor relevance for the pathogenesis of invasive aspergillosis. In addition, microscopic examination of aspergilli penetrating vessel walls did not reveal obvious lysis of wall proteins, thus emphasizing a mechanical disruption of fibrillar proteins by the growing hyphae. However, a strictly localized proteolysis at the tips of growing hyphae caused by wall associated proteinases might be involved. Candidates for such a mechanism are the activities of aspartic and serine proteinases which we have discovered in the cell wall fraction of A. fumigatus.