Expression of extracellular acid proteinase by proteolytic Candida spp. during experimental infection of oral mucosa

Abstract

We traced an acid proteinase from Candida spp. in the initial stages of the pathogenesis of the mycosis. On infection of human buccal mucosa, proteinase antigens were detected by immuno-scanning electron microscopy on the surface of adhering blastoconidia and invading filamentous cells of C. albicans serotype A. Proteinase antigens were also present on blastoconidia of C. albicans serotype B, but were missing on filamentous cells of this serotype. Proteolytic isolates of C. tropicalis behaved like C. aLbicans serotype A. An isolate of C. parapsiosis did not express the proteinase antigen under conditions of this study. After infection of mucosa, culture medium of C. albicans or C. tropicalis showed a time-dependent accumulation of acid proteolytic activity, indicating that the visualized antigens represent active proteinase. No such activity was detected in the medium of C. parapsilosis. Preliminary experiments with the proteinase inhibitor pepstatin A revealed an 89% reduction of mucosal adherence of C. albicans (serotype A). These results suggest that Candida proteinase is involved in fungal attachment. The pattern of adherence reflects the differential expression of secretory proteinase by different candidal strains.

A Role of Secreted Proteinase of Candida albicans for the Invasion of Chick Chorio‐Allantoic Membrane

“…We therefore conclude that the secreted fungal proteinase may disorganize the ectoderm tissue at an early stage of infection. Recent reports that Candida proteinase was demonstrated in the initial stage during experimental infection of oral mucosa (2) and that this enzyme may facilitate adhesion/invasion events on the tissue (25) would support our results in this study.…”

Altered adherence in strains of Candida albicans harbouring null mutations in secreted aspartic proteinase genes

“…Sap production in stationary phase yeast cells is likely to occur at a basal level [11,29] and other aspects of the prevailing conditions in the adhesion assays are likely to suboptimal for the expression of the various Sap isoenzymes. Several previous reports have demonstrated pepstatin A inhibition of adherence for cells grown in media that would not be expected to be proteinase-inducing [17,19,30] again suggesting that some degree of proteinase secretion occurs even in non-protein-containing media. In the present study the changes in relative adherence measured for the various Sap isoenzymes also provides indirect evidence that SAP gene expression does occur under the conditions examined.…”

“…Most studies have emphasised the likely role of these proteinases in facilitating penetration via tissue necrosis or in the destruction of immunoglobulins. However, the Sap inhibitor pepstatin A has been reported to block invasion of host tissue by hyphal cells at neutral pH [17] and to reduce the adherence of yeast cells to various cell types [18,19], suggesting a possible non-enzymatic role for the enzymes in adherence. Therefore we used various SAP gene null mutants to investigate the putative role of Saps in the adhesion of C. albicans to three di¡erent substrates: glass coated with poly-L-lysine, or a layer of endothelial cell basement membrane components (Matrigel) and to human buccal epithelial cells (BECs).…”

HIV-1 and its transmembrane protein gp41 bind to differentCandidaspecies modulating adhesion

“…Recent studies suggest that certain Saps, belonging to another important set of virulence factors [17,21,24,38], not only facilitate tissue penetration but also promote its prerequisite, the fungal attachment to epithelial and endothelial cells [21,39,40], in part by reversing the inhibitory e¡ect of host factors, e.g. that of mucin [41].…”