Inhibition of growth and secreted aspartyl proteinase production in Candida albicans by lysozyme

Lysozyme (muramidase) is a non-specific, antimicrobial protein ubiquitous i n human mucosal secretions such as saliva. Although its antibacterial and a ntifungal 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 isolat es of C. albicans were cultured in YCB-BSA medium with various concentratio ns of lysozyme to examine its effect on yeast cell growth, ultrastructural cellular topography and extracellular and intracellular Sap concentration a nd activity. Lysozyme was candidacidal at high concentrations and decreased significantly the extracellular Sap concentration at sublethal doses, acco mpanied by intracellular accumulation of the enzyme. At low concentrations of lysozyme (c. 10 mu g/ml), Sap activity decreased more than two-fold and Sap concentration decreased five-fold without any appreciable effect on cel l growth or viability. Ultrastructural investigations showed ballooned cell s and cells with invaginations (expecially present near bud scars), indicat ing that cell-wall components may be possible targets for this enzyme. All concentrations of lysozyme tested were well within physiologically attainab le levels. These data suggest that lysozyme has, at least, a bimodal action on C. albicans, killing the organism at higher concentrations and modulati ng Sap metabolism at lower concentrations.