ASPERGILLUS PROTEINASES AND THEIR INTERACTIONS WITH HOST TISSUES

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 fo cused on proteinases produced by these organisms and their possible ro les in the pathogenesis of infection. Both species produce alkaline se rine proteinases (ALP) and metalloproteinases during the course of inf ection based on immunohistochemistry of experimental lesions and serol ogic response of patients. These enzymes can be shown to degrade numer ous biologically relevant targets, including elastin, collagen, lamini n, fibrinogen, and iC3b. Physicochemical properties, immunoreactivitie s, and amino acid sequences of the ALP of A. fumigatus and A. flavus s how that these two enzymes are closely related. The metalloproteinases , however, appear to represent members of a small family of similar en zymes. Finally, although studies using conventionally produced mutants support roles for these hydrolases as virulence factors in aspergillo sis, similar studies using strains of A. fumigatus in which the enzyma tic activity has been ablated through gene disruption do not reveal di fferences in virulence between the wild-type strains and the mutants.