How Does It Kill?: Understanding the Candidacidal Mechanism of Salivary Histatin 5

• Published in: Eukaryotic cell Vol. 13; no. 8; pp. 958 - 964
• Main Authors: Puri, Sumant, Edgerton, Mira
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.08.2014
• Subjects: Amino Acid Sequence; Candida albicans; Candida albicans - physiology; Candidiasis - immunology; Candidiasis - microbiology; Cell Membrane Permeability; Histatins - physiology; Host-Pathogen Interactions; Humans; Immunity, Innate; MAP Kinase Signaling System; Microbial Viability; Minireviews; Molecular Sequence Data; Protein Binding; Saliva - metabolism
• ISSN: 1535-9778; 1535-9786; 1535-9786
• DOI: 10.1128/EC.00095-14

Histatins are salivary cationic peptides that provide the first line of defense against oral candidiasis caused by Candida albicans . This minireview presents a critical evaluation of our knowledge of the candidacidal mechanism of histatin 5 (Hst 5). Hst 5 is the most potent among all histatin family members with regard to its antifungal activity. The mode of action of Hst 5 has been a subject of intense debate. Unlike other classical host innate immune proteins, pore formation or membrane lysis by Hst 5 has largely been disproven, and it is now known that all targets of Hst 5 are intracellular. Hst 5 binds C. albicans cell wall proteins (Ssa1/2) and glycans and is taken up by the cells through fungal polyamine transporters in an energy-dependent manner. Once inside the fungal cells, Hst 5 may affect mitochondrial functions and cause oxidative stress; however, the ultimate cause of cell death is by volume dysregulation and ion imbalance triggered by osmotic stress. Besides these diverse targets, a novel mechanism based on the metal binding abilities of Hst 5 is discussed. Finally, translational approaches for Hst 5, based on peptide design and synergy with other known drugs, are considered a step forward for bench-to-bed application of Hst 5.