Extracellular proteinases of Candida species pathogenic yeasts

Abstract

The increased incidence of severe disseminated infections caused by the opportunistic yeast-like fungi Candida spp. highlights the urgent need for research into the major virulence factors of these pathogens-extracellular aspartic proteinases of the candidapepsin and yapsin families. Classically, these enzymes were considered to be generally destructive factors that damage host tissues and provide nutrients for pathogen propagation. However, in recent decades, novel and more specific functions have been suggested for extracellular candidal proteinases. These include contributions to cell wall maintenance and remodeling, the formation of polymicrobial biofilms, adhesion to external protective barriers of the host, the deregulation of host proteolytic cascades (such as the complement system, blood coagulation and the kallikrein-kinin system), a dysregulated host proteinase-inhibitor balance, the inactivation of host antimicrobial peptides, evasion of immune responses and the induction of inflammatory mediator release from host cells. Only a few of these activities recognized in Candida albicans candidapepsins have been also confirmed in other Candida species, and characterization of Candida glabrata yapsins remains limited.

New Insights in Candida albicans Innate Immunity at the Mucosa: Toxins, Epithelium, Metabolism, and Beyond

“…Additionally, many other secreted elements are actively involved in C. albicans pathogenesis, including hydrolytic enzymes and the recently described toxin candidalysin. Among the hydrolytic enzymes, secreted aspartyl proteinases (SAPs) are the most well-known (Naglik et al, 2003;Rapala-Kozik et al, 2018). This group of enzymes is formed of ten members that are either secreted (Sap1-8p) or kept anchored to the cell wall (Sap9-10p) (Albrecht et al, 2006).…”

“…This group of enzymes is formed of ten members that are either secreted (Sap1-8p) or kept anchored to the cell wall (Sap9-10p) (Albrecht et al, 2006). Notably, they degrade relevant components of the immune response in the mucosae, as cadherins, complement system molecules or immunoglobulins (Naglik et al, 2003;Rapala-Kozik et al, 2018). However, while these proteins seem to help C. albicans to evade the immune responses, their relation to epithelial damage and mucosal invasion is less clear.…”

Newly Emerging Candida Specie: Should Clinicians and Mycologist be Concerned?

“…Extracellular hydrolytic enzymes produced by Candida species is an important virulence trait contributing to its pathogenicity. The ability to produce lytic enzymes has been demonstrated in C. auris isolates, and the production of these enzymes is strain dependent [23,24]. The most common virulence associated enzymes are the proteinase.…”

“…The most common virulence associated enzymes are the proteinase. hemolysins, lipases and phospholipases, which play crucial roles in the virulence of the species [23,24]. These enzymes are considered to play a role in the degradation of host tissue to provide nutrients for pathogen propagation.…”

“…These enzymes are considered to play a role in the degradation of host tissue to provide nutrients for pathogen propagation. Protienases has in recent times been associated with cell wall maintenance, the formation of polymicrobial biofilms, adhesin to external protective barriers of the host, deregulation of the complement system, inactivation of host antimicrobial peptides, evasion of the immune responses and the induction of inflammatory mediator release from host cells [23,24,25].…”