Calcium blocks fungicidal activity of human salivary histatin 5 through disruption of binding with Candida albicans.
Salivary histatin 5 (Hst 5) kills the fungal pathogen C. albicans via a mechanism that involves binding and subsequent efflux of cellular ATP. Our aims were to identify inorganic ions found in saliva that influence Hst 5 fungicidal activity. Increasing ionic strength with relevant salivary anions (Cl(-) and CO(3)(-)) did not reduce Hst 5 binding or uptake by yeast cells, but reduced the Hst-induced efflux of ATP. Extracellular MgCl(2) (25 mM) maximally inhibited 30-40% of Hst 5 killing with 40% reduction in ATP efflux, while pre-treatment of cells with only 2 mM CaCl(2) inhibited 80-90% of killing, and prevented ATP efflux. Loss of fungicidal activity by the addition of CaCl(2) or MgCl(2) was a result of inhibition of binding of Hst 5 to C. albicans cells. Calcium is a potent inhibitor of Hst 5 candidacidal activity at physiological concentrations and may be the primary salivary ion responsible for the masking effect of saliva.
Dong
J
J
Department of Oral Biology, State University of New York, Buffalo, NY 14214, USA. edgerto@buffalo.edu
Vylkova
S
S
Li
X S
XS
Edgerton
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000935:Antifungal Agents / Q000037:antagonists & inhibitors*; D002118:Calcium / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects*; D002254:Carbonates / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D005434:Flow Cytometry; D054808:Histatins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015636:Magnesium Chloride / Q000494:pharmacology; D009994:Osmolar Concentration; D011485:Protein Binding / Q000187:drug effects; D012471:Salivary Proteins and Peptides / Q000037:antagonists & inhibitors*
D000935:Antifungal Agents; D002254:Carbonates; D002712:Chlorides; C068075:HTN3 protein, human; D054808:Histatins; D012471:Salivary Proteins and Peptides; D015636:Magnesium Chloride; D000255:Adenosine Triphosphate; D002122:Calcium Chloride; D002118:Calcium