title: 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. 10 microg/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 (especially 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.
authors.affiliation: Faculty of Dentistry, University of Hong Kong, Hong Kong.
authors.forename: T
authors.initials: T
authors.lastname: Wu
authors.affiliation: Faculty of Dentistry, University of Hong Kong, Hong Kong.
authors.forename: L P
authors.initials: LP
authors.lastname: Samaranayake
authors.affiliation: Faculty of Dentistry, University of Hong Kong, Hong Kong.
authors.forename: W K
authors.initials: WK
authors.lastname: Leung
authors.affiliation: Department of Biochemistry, Massey University, Palmerston North, New Zealand.
authors.forename: P A
authors.initials: PA
authors.lastname: Sullivan
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015153:Blotting, Western; D002176:Candida albicans / Q000166:cytology / Q000201:enzymology* / Q000648:ultrastructure; D002455:Cell Division / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000201:enzymology; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009113:Muramidase / Q000378:metabolism / Q000494:pharmacology*; D013045:Species Specificity
chemical_list: D000890:Anti-Infective Agents; D017077:Culture Media, Conditioned; D009113:Muramidase; D016282:Aspartic Acid Endopeptidases