Histatin

Histatin is a family of small, histidine-rich cationic peptides found in human saliva. Named for their abundance of histidine, histatins contribute to the oral chemical defense system. Members described include histatin-1, histatin-3, and histatin-5, with histatin-5 the most potent antifungal member.

Histatins are secreted by the major salivary glands and accumulate in saliva. They are rich in positively charged residues, which enhances interactions with microbial membranes and cell walls. They can be further cleaved by salivary proteases into active fragments, which may retain antimicrobial activity.

Antimicrobial activity: Histatins exhibit antimicrobial effects, especially histatin-5 against Candida species such as Candida albicans. They also show activity against some bacteria and may reduce biofilm formation. In addition to antimicrobial effects, histatins contribute to wound healing and mucosal repair in the oral cavity.

Mechanistically, histatin-5 is thought to be taken up by fungal cells through energy-dependent transporters and to disrupt mitochondrial function, leading to ATP depletion and cell death. Other histatins may act by targeting membranes or by metal ion chelation via their histidine residues, contributing to their antimicrobial effects.

Clinical relevance: Histatins are considered part of the innate defense of the mouth and are being explored as templates for therapeutic antifungal peptides. Challenges to therapeutic use include proteolytic degradation in saliva, stability in the oral environment, and delivery methods. Research continues on designing histatin-derived peptides and mimetics with improved stability and antifungal potency.