Salivary histatin 5 and its similarities to the other antimicrobial proteins in human saliva.
Non-immune salivary proteins--including lactoperoxidase, lysozyme, lactoferrin, and histatins--are key components of the innate host defense system in the oral cavity. Many antimicrobial proteins contain multiple functional domains, with the result that one protein may have more than one mechanism of antimicrobial activity. These domains may be separated by proteolytic cleavage, creating smaller proteins with functional antimicrobial activity in saliva as described for lysozyme, lactoferrin, and histatins. These small cationic proteins then exert cytotoxic activity to oral bacteria and fungi. Salivary histatin 5 initiates killing of C. albicans through binding to yeast membrane proteins and non-lytic release of cellular ATP. Extracellular ATP may then activate fungal ATP receptors to induce ultimate cell death. This mechanism for fungal cytotoxicity may be shared by other antimicrobial cationic proteins. Microbicidal domains of salivary and host innate proteins should be considered as potential therapeutic agents in the oral cavity.
Edgerton
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Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, 14214, USA. Edgerto@buffalo.edu
Koshlukova
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000378:metabolism; D016923:Cell Death; D054808:Histatins; D006801:Humans; D007781:Lactoferrin / Q000502:physiology; D007784:Lactoperoxidase / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D009113:Muramidase / Q000502:physiology; D011485:Protein Binding; D011506:Proteins / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D012471:Salivary Proteins and Peptides / Q000502:physiology*; D000099053:Histidine-Rich Glycoprotein
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; C068075:HTN3 protein, human; D054808:Histatins; D008565:Membrane Proteins; D011506:Proteins; D018048:Receptors, Purinergic P2; D012471:Salivary Proteins and Peptides; D000099053:Histidine-Rich Glycoprotein; D000255:Adenosine Triphosphate; D007784:Lactoperoxidase; D009113:Muramidase; D007781:Lactoferrin