Aspartic Proteases of Human Pathogenic Fungi are Prospective Targets for the Generation of Novel and Effective Antifungal Inhibitors

Andre Luis Souza dos      Santos

doi:10.2174/157340811796575281

Abstract

Fungi can cause life-threatening diseases, particularly in patients with weakened immunological systems. Although treatment options are available for these individuals, dose-limiting toxicity and the appearance of drug-resistant microorganisms are growing problems. Detailed structural and functional characterization of fungal proteases has led to novel insights into the workings of these fascinating catalytic machines. Identification and characterization of proteasemediated processes in human pathogenic fungi is progressing at a rapid rate. In these microorganisms, aspartic-type proteases carry out “housekeeping” tasks common to many eukaryotes as well as functions highly specific to the fungal life cycles. Consequently, the possibility of developing selective inhibitors of key aspartic proteases of pathogenic fungi into novel chemotherapeutic strategies is being vigorously explored. The present review describes the knowledge in the area of aspartic proteases produced by human fungal pathogens. As well, the effects of aspartic proteolytic inhibitors on multiple vital processes of fungal cells, with special emphasis on their roles to arrest fungal development and virulence, will be presented and discussed.

Keywords: Aspartic proteases, proteolytic inhibitors, human pathogenic fungi, antifungal agents, HIV, chemotherapy, immunological systems, diabetes mellitus, phagocyte dysfunction, malnutrition