title: Candida albicans Shed Msb2 and Host Mucins Affect the Candidacidal Activity of Salivary Hst 5.
abstract: Salivary Histatin 5 (Hst 5) is an antimicrobial peptide that exhibits potent antifungal activity towards Candida albicans, the causative agent of oral candidiasis. However, it exhibits limited activity in vivo, largely due to inactivation by salivary components of both host and pathogen origin. Proteins secreted by C. albicans during infection such as secreted aspartyl proteases (Saps) and shed mucin Msb2 can reduce Hst 5 activity; and human salivary mucins, while suggested to protect Hst 5 from proteolytic degradation, can entrap peptides into mucin gels, thereby reducing bioavailability. We show here that Sap6 that is secreted during hyphal growth reduces Hst 5 activity, most likely a result of proteolytic degradation of Hst 5 since this effect is abrogated with heat inactivated Sap 6. We further show that just like C. albicans shedding Msb2, mammalian mucins, fetuin and porcine gut mucin (that is related to salivary mucins), also reduce Hst 5 activity. However, we identify mucin-like protein-induced changes in C. albicans cell morphology and aggregation patterns, suggesting that the effect of such proteins on Hst 5 cannot be interpreted independently of their effect on yeast cells.
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY 14214, USA. spuri@buffalo.edu.
authors.forename: Sumant
authors.initials: S
authors.lastname: Puri
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY 14214, USA. jmfriedm@buffalo.edu.
authors.forename: Justin
authors.initials: J
authors.lastname: Friedman
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY 14214, USA. darpansa@buffalo.edu.
authors.forename: Darpan
authors.initials: D
authors.lastname: Saraswat
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY 14214, USA. rohitash@buffalo.edu.
authors.forename: Rohitashw
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY 14214, USA. rli7@buffalo.edu.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, Buffalo, NY 14214, USA. dmruszaj@buffalo.edu.
authors.forename: Donna
authors.initials: D
authors.lastname: Ruszaj
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY 14214, USA. edgerto@buffalo.edu.
authors.forename: Mira
authors.initials: M
authors.lastname: Edgerton
keywords: Candida albicans; Histatin 5; mucins; oral candidiasis; saliva; secreted  aspartyl proteases