Aspartic proteinases of Candida spp.: role in pathogenicity and antifungal resistance

Abstract

Fungal infections represent a serious health risk as they are particularly prevalent in immunocompromised individuals. Candida spp. pathogenicity depends on several factors and secreted aspartic proteinases (Sap) are considered one of the most critical factors as they are associated with adhesion, invasion and tissue damage. The production of proteinases is encoded by a family of 10 genes known as SAP, which are distributed differently among the species. The expression of these genes may be influenced by environmental conditions, which generally result in a higher fungal invasive potential. Non-pathogenic Candida spp. usually have fewer SAP genes, which are not necessarily expressed in the genome. Exposure to subinhibitory concentrations of antifungal agents promotes the development of resistant strains with an increased expression of SAP genes. In general, Candida spp. isolates that are resistant to antifungals show a higher secretion of Sap than the susceptible isolates. The relationship between Sap secretion and the susceptibility profile of the isolates is of great interest, although the role of SAPs in the development of resistance to antifungal agents remains still unclear. This review is the first one to address these issues.

Relationship between the Antifungal Susceptibility Profile and the Production of Virulence-Related Hydrolytic Enzymes in Brazilian Clinical Strains ofCandida glabrata

“…Moreover, secretion of hydrolytic enzymes has the ability to regulate Candida spp. antifungal drug resistance [46]. …”

“…These enzymes control several steps in innate immune evasion, and they degrade proteins related to immunological defense such as antibodies, complement, and citokines, allowing the fungus to escape from the first line of host defenses [48]. Moreover, a study developed by Silva et al [46] suggests that naturally resistant Candida spp. or isolates that have developed resistance after prolonged exposure to drugs may present an increase in the secretion pattern and proteolytic activity of secreted aspartic proteases (SAP), but more studies are needed to elucidate its relation.…”

“…In our study, most strains of C. glabrata were classified as good aspartic protease producers. However, C. glabrata does not possess classical SAP genes in its genome [46, 49]. Probably the enzymatic degradation of albumin verified herein may be due to the production of yapsins.…”

Antifungal and antiviral products of marine organisms

“…Hitherto, there are several major antifungal drugs targeting C. albicans as follows: pyrimidines like 5-fluorocytosine, polyenes including amphotericin B and nystatin, azoles such as fluconazole, and echinocandins such as caspofungin. Due to drug resistance encountered during treatments with all four types of drugs and the reported side effects, a search for more potential antifungal agents is warranted (Bondaryk et al 2013; Geronikaki et al 2013; Hamill 2013; Silva et al 2014). Lung infections caused by non- Aspergillus molds are increasing in specific populations, and new problems of susceptibility and resistance have emerged (Paiva and Pereira 2013).…”

Screening of Compounds from an FDA-Approved Drug Library for the Ability to Inhibit Aspartic Protease Secretion from the Pathogenic Yeast Candida albicans

“…To cause an infection, the pathogen invades host tissues. C. albicans secretes aspartic protease (Sap) as a hydrolase into the host tissue [4][5]. C. albicans Sap plays an important role in not only host tissue invasion but also inactivation of complement, defensin, and lactoferrin, which are involved in host defense.…”