Protein Engineering Approaches to Improve the Therapeutic Potential of Histatin-5 for Candida albicans Infections
Leissa, Jesse Alton
Karlsson, Amy J
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The salivary peptide histatin 5 has been studied as a novel therapeutic to address rising drug resistance and limited therapeutics for treating infections caused by the fungal pathogen Candida albicans. While histatin 5 possesses antifungal activity, degradation from secreted aspartic proteases produced by C. albicans hinders its potential. To develop a strategy that will identify variants of histatin 5 with improved proteolytic stability, the peptide was integrated into a yeast surface display system, and the proteolytic degradation conditions were optimized to improve the resolution between proteolytically stable (K11RK17R) and proteolytically susceptible (K13L) variants. Additionally, histatin 5 and K11RK17R were embedded in polyelectrolyte multilayer films (PEMs) to investigate their ability to prevent biofilm formation on surfaces. Significant biofilm formation was prevented at high concentrations of K11RK17R, while histatin 5 encouraged biofilm formation. My results support the therapeutic potential of histatin 5 and will enable the design of improved peptide-based therapeutic approaches.