Histatin-5 is a 24-amino-acid histidine-rich cationic peptide (sequence: DSHAKRHHGYKRKFHEKHHSHRGY, MW ~3036 g/mol) found in human saliva. It is the most potent antifungal member of the histatin family, which comprises at least 12 peptides secreted by parotid and submandibular salivary glands. Histatin-5 is a key component of innate oral antifungal defense, particularly against Candida albicans.
Category: Antimicrobial / Immune. Evidence rating: D (animal/preclinical only).
Clinical status: Endogenous peptide. No therapeutic product in development. Studied as a template for antifungal drug design.
Histatin-5 kills Candida albicans through a non-lytic, energy-dependent mechanism. The peptide binds to the fungal cell wall protein Ssa1/2 (a heat shock protein), is internalized via polyamine transporters, and targets mitochondria. Inside the cell, it causes mitochondrial membrane…
Safety considerations: Endogenous component of normal human saliva (present at 15-30 micromolar in parotid saliva); No exogenous therapeutic products exist for safety evaluation; Activity reduced by physiological salt concentrations and salivary mucins.
Reviewed by the PeptideAtlas Editorial Team.
| Amino-acid sequence | DSHAKRHHGYKRKFHEKHHSHRGY |
|---|---|
| Molecular weight | ~3036 g/mol |
| Production method | synthetic |
| Anti-doping status | not-listed |
| US regulatory status | Endogenous human peptide. No therapeutic product. Not subject to FDA drug approval. |
Related peptides: LL-37, Beta-Defensins, Alpha-Defensins.
Histatin-5 is the most potent antifungal peptide in human saliva and provides innate defense against oral Candida colonization. People with reduced salivary flow (dry mouth) or reduced histatin production (HIV/AIDS, Sjogren syndrome) are more susceptible to oral thrush.
Researchers are exploring histatin-5 derivatives and analogs with improved stability and salt tolerance as potential topical antifungal agents, particularly for oral candidiasis. No products have reached clinical trials.
Unlike azole or echinocandin antifungals, histatin-5 kills Candida through a unique mechanism involving mitochondrial targeting and energy-dependent ATP release. This mechanism may be less susceptible to conventional antifungal resistance mechanisms.