Inhibition of Growth and Secreted Aspartyl Proteinase Production in Candida Albicans by Lysozyme

Abstract

Lysozyme (muramidase) is a non-specific, antimicrobial protein ubiquitous in human mucosal secretions such as saliva. Although its antibacterial and antifungal activities are well recognised, there are no data on the specific concentrations necessary to affect the growth of Candida albicans or about the effect of lysozyme on the production of secreted aspartyl proteinase (Sap), a putative virulence factor of C. albicans. Five Sap-producing isolates of C. albicans were cultured in YCB-BSA medium with various concentrations of lysozyme to examine its effect on yeast cell growth, ultrastructural cellular topography and extracellular and intracellular Sap concentration and activity. Lysozyme was candidacidal at high concentrations and decreased significantly the extracellular Sap concentration at sublethal doses, accompanied by intracellular accumulation of the enzyme. At low concentrations of lysozyme (c. lOpg/ml), Sap activity decreased more than two-fold and Sap concentration decreased five-fold without any appreciable effect on cell growth or viability. Ultrastructural investigations showed ballooned cells and cells with invaginations (expecially present near bud scars), indicating that cell-wall components may be possible targets for this enzyme. All concentrations of lysozyme tested were well within physiologically attainable levels. These data suggest that lysozyme has, at least, a bimodal action on C. albicans, killing the organism at higher concentrations and modulating Sap metabolism at lower concentrations.

Pulmonary immune responses induced in BALB/c mice by Paracoccidioides brasiliensis conidia

“…Furthermore, we observed an increase of lysozyme expression in the lungs of mice infected with P. brasiliensis conidia during the early stages of infection (1-4 days), with the expression concentrating mainly on PMNs and macrophages with a parallel decrease in the number of fungal propagules (Gonzalez et al, unpublished data). The microbicidal effect of lysozyme has been demonstrated against C. albicans and H. capsulatum [106,125,126]. These results suggest that in vivo, lysozyme could well be one of the molecules participating in the control of P. brasiliensis infection.…”

Simple Method for Screening Candida Species Isolates for the Presence of Secreted Proteinases: a Tool for the Prediction of Successful Inhibitory Treatment

“…In liquid protein-supplemented cultures of C. albicans, the characteristic drop in pH associated with Sap production has been observed by others (29). To examine possible pH changes during Candida culture growth on hemoglobin plates, we added bromphenol blue to the medium.…”

Dialysis Unmasks the Fungicidal Properties of Glandular Salivary Secretions

“…Another salivary antifungal agent is lysozyme, which has a bimodal action on C. albicans. At higher concentrations, it has a direct killing effect, while at lower concentrations, it inhibits the proteolytic activity of secreted aspartyl proteinases, enzymes that facilitate the penetration of keratinocytes and are therefore considered important virulence factors of C. albicans (30). Furthermore, saliva contains histatins, a family of small cationic, histidine-rich peptides which display fungistatic (23) and fungicidal (7,11,21) activities against C. albicans and other fungi and inhibit the conversion of C. albicans from blastospores into the more virulent germinated form (27,31).…”