Statherin induces transition of hyphae to yeast in Candida albicans

Candida albicans is an opportunistic pathogen living as a benign commensal in a variety of body locations, notably the oral cavity, genitalia and gastrointestinal tract. However, when the host immune system is compromised C.albicans can cause infection. One of the virulence factors of C.albicans is that it undergoes a morphological transition from yeast cells to hyphae filaments which is considered the most invasive form of the fungus. Objectives: to investigate the effect of saliva on hyphae growth of C.albicans. Methods: C.albicans hyphae were inoculated in RPMI medium with whole saliva, parotid saliva or buffer mimicking the saliva ion composition and cultured 18 hours at 37ºC under aerobic conditions with 5% CO2. Hyphae formation was studied microscopically. Saliva substances were purified by reverse phase HPLC. Peptides were synthesized by solid phase peptide synthesis using F-moc chemistry with a MilliGen 9050 peptide synthesizer. Results: whole saliva and parotid saliva induced transition to yeast growth whereas the culture with buffer remained in the hyphae form. The salivary component in the active fraction was identified by HPLC as statherin, a phosphoprotein of 43 amino acids involved in remineralization of the teeth. Synthetically made statherin induced transition of hyphae to yeast. St6-43, in which 5 amino acids at the negatively charged N-terminal site (DpSpSEE) were deleted, showed stronger yeast inducing activity and binding to C.albicans compared to the full length statherin. St6-18 showed binding to C.albicans but did not induce transition of hyphae to yeast whereas St20-43 showed neither binding nor induced of transition to yeast. Conclusions: statherin induces transition of C.albicans hyphae to yeast which may be considered as a novel salivary defense system against candidiasis.