Characterization of a secretory proteinase of Candida parapsilosis and evidence for the absence of the enzyme during infection in vitro

Abstract

The opportunistic yeastlike fungi of the genus Candida comprise three species which are proteolytic in vitro. Among them, C. albicans and C. tropicalis are of foremost medical importance. However, a strict correlation between extracellular proteolytic activity and virulence is opposed by the low virulence of the third proteolytic species, C. parapsilosis. We purified the secretory acid proteinase of C. parapsilosis (clinical isolate 265). The enzyme is a carboxyl proteinase (EC 3.4.23) like all other secretory Candida proteinases handled so far. Proteinase 265 is distinguished by a lower molecular weight (approximately 33,000); it has increased hydrophobicity, which accounts for inhibition of the enzyme by hemin, and required the presence of nonionic detergent in the initial steps of purification. The enzyme already undergoes alkaline denaturation at neutrality. Its activity is thus confined to the acid microenvironment of the fungal cel wall. Within this range, the enzyme may degrade immunoglobulins like immunoglobulin Al (IgAl), IgA2, and secretory IgA. No indication was found for glycosylation of proteinase 265 and the related enzyme of C. albicans CBS 2730. However, the comparable proteinase of C. tropicalis 293 was identified as a manno protein. Antiserum against proteinase 265 cross-reacted strongly with corresponding enzymes from other Candida species. Antisera against proteinases of C. albicans and C. tropicalis reacted only weakly with proteinase 265. Thus, secretory Candida proteinases are likely to possess common and species-specific antigenic sites. In contrast to C. albicans, infection of phagocytes by C. parapsilosis 265 was not accompanied by secretion of fungal proteinase. This lack of induction of the enzyme under conditions of infection may account for the low virulence of most isolates of C. parapsiosis. Among the yeastlike fungi of the genus Candida, C. albicans is of foremost medical importance as an opportunistic organism, followed by C. tropicalis and possibly C. parapsilosis (1, 3). These three species are distinguished by the secretion of acid proteinase in vitro. Candida proteinases were first discovered in C. albicans by Staib (37). Subsequently, extracellular proteolytic activity was also detected among the majority of isolates of C. tropicalis and C. parapsilosis (17, 36). Considerable evidence subsequently accrued indicating that secretory proteinases are factors in the virulence of C. albicans (15, 17, 19, 20a, 32, 38). Such correlation may also exist among isolates of C. tropicalis (4), but it is missing in C. parapsilosis. Isolates of this species are mostly proteolytic in vitro (17, 36, 39), but they possess only low virulence in vitro (4) and in mice (2). In humans, deep mycoses due to C. parapsilosis had a better prognosis than those that were caused by other Candida species (6). To elucidate the discrepancy between the high proteolytic activity in vitro and the low virulence of C. parapsilosis, we purified and characterized a secretory proteinase of this species, thus allowing...

The effect of sodium hypochlorite on potential pathogenic traits of Candida albicans and other Candida species

“…Once adhered to surfaces in the oral cavity, Candida cells may invade tissues. This process has been linked to the ability of C. albicans strains to produce hyphae and proteinase (11,28,32,43), and the data in the current study agree with these findings. Other investigators (30) have demonstrated that hyphae produce proteinases at their growing tips.…”

Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae

“…However, only one product has been identified as an extracellular aspartic protease. This protease has been partially characterized [29,30]. Fusek et al [31] isolated two aspartic proteases secreted by C. parapsilosis.…”

Basidiomycete metabolites attenuate virulence properties of Candida albicans in vitro

“…are divergent. 31,32 Taken together, the development of broad Sap isoenzyme specific inhibitors is plausible and effective during different stages of infection, as well as lucrative. Sap-specific inhibition is also required to circumvent the involvement of endogenic proteinases.…”