Aspergillusproteinases and their interactions with host tissues

Abstract

Invasive aspergillosis is a life-threatening infection that is caused primarily by the species Aspergillus fumigatus and A. flavus, both of which are highly angioinvasive. From this observation, interest has focused on proteinases produced by these organisms and their possible roles in the pathogenesis of infection. Both species produce alkaline serine proteinases (ALP) and metalloproteinases during the course of infection based on immunohistochemistry of experimental lesions and serologic response of patients. These enzymes can be shown to degrade numerous biologically relevant targets, including elastin, collagen, laminin, fibrinogen, and iC3b. Physicochemical properties, immunoreactivities, and amino acid sequences of the ALP of A. fumigatus and A. flavus show that these two enzymes are closely related. The metalloproteinases, however, appear to represent members of a small family of similar enzymes. Finally, although studies using conventionally produced mutants support roles for these hydrolases as virulence factors in aspergillosis, similar studies using strains of A. fumigatus in which the enzymatic activity has been ablated through gene disruption do not reveal differences in virulence between the wild-type strains and the mutants. Key words: aspergillosis, proteinase, pathogenesis.