Contribution of Aspartic Proteases in Candida Virulence. Protease Inhibitors against Candida Infections

Curr Protein Pept Sci. 2017;18(10):1050-1062. doi: 10.2174/1389203717666160809155749.

Abstract

Candida species are the major opportunistic human pathogens accounting for 70-90% of all invasive fungal infections. Candida spp, especially C. albicans, are able to produce and secrete hydrolytic enzymes, particularly aspartic proteases (Saps). These enzymes production is an evolutionary adaptation of pathogens to utilize nutrients and survive in host. Sap1-10 are believed to contribute to the adhesion and invasion of host tissues through the degradation of cell surface structures. Aspartic proteases control several steps in innate immune evasion and they degrade proteins related to immunological defense (antibodies, complement and cytokines), allowing the fungus to escape from the first line of host defense. The existing ways to identify potential drug targets rely on specific subset like virulence genes, transcriptional and stress response factors. Candida virulence factors like Sap isoenzymes can be pivotal targets for drug development. The identification of mechanism of a non-canonical inflammasome exerted by Saps could open novel therapeutic strategies to dampen hyperinflammatory response in candidiasis.

Keywords: Candida; Sap1-10; enzymes; fungal infections; inhibitors; pathogenesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology
  • Aspartic Acid Endopeptidases / antagonists & inhibitors
  • Aspartic Acid Endopeptidases / genetics*
  • Aspartic Acid Endopeptidases / metabolism
  • Candida albicans / drug effects
  • Candida albicans / enzymology
  • Candida albicans / genetics*
  • Candida albicans / pathogenicity
  • Candidiasis / drug therapy
  • Candidiasis / immunology*
  • Candidiasis / microbiology
  • Candidiasis / pathology
  • Disease Models, Animal
  • Fungal Proteins / antagonists & inhibitors
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Gene Expression
  • Immune Evasion
  • Immunity, Innate
  • Opportunistic Infections / drug therapy
  • Opportunistic Infections / immunology*
  • Opportunistic Infections / microbiology
  • Opportunistic Infections / pathology
  • Protease Inhibitors / pharmacology
  • Virulence
  • Virulence Factors / antagonists & inhibitors
  • Virulence Factors / genetics*
  • Virulence Factors / metabolism

Substances

  • Antifungal Agents
  • Fungal Proteins
  • Protease Inhibitors
  • Virulence Factors
  • Aspartic Acid Endopeptidases