Aspartyl proteases in human pathogenic fungi: Roles in physiology and virulence

Abstract

Human fungal pathogens possess an armory of virulence factors that empowers successful colonization and infection of diverse host niches and evasion of the host defense mechanisms under favorable conditions. Of these determinants, proteolytic activity of extracellular aspartyl proteases plays a pivotal role in the fungal virulence. Fungal aspartyl proteases constitute a family of highly similar enzymes with overlapping yet distinct substrate specificities which fall broadly into two types, the glycosylphosphatidylinositol (GPI)-linked yeast aspartyl proteases (Yapsins) and the secreted aspartyl proteases (Saps). The present chapter discusses the fungal multi-gene families encoding extracellular aspartyl proteases, the structure-function relationships of aspartyl proteases and the regulation of their proteolytic activity in response to various environmental cues. This chapter also summarizes the information available on the potential physiological substrates of aspartyl proteases with respect to their possible role in adaptation to adverse environmental conditions and in interaction with the host cells with a special focus on the contribution of the GPI-anchored aspartyl proteases to the pathogenesis of Candida glabrata. The final section of the chapter provides an outlook on how functional proteomics approaches could advance our understanding of the physiological functions of extracellular fungal aspartyl proteases.