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Eukaryot Cell. 2014 Aug;13(8):958-64. doi: 10.1128/EC.00095-14. Epub 2014 Jun 20.

How does it kill?: understanding the candidacidal mechanism of salivary histatin 5.

Author information

1
Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, New York, USA.
2
Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, New York, USA edgerto@buffalo.edu.

Abstract

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.

PMID:
24951439
PMCID:
PMC4135785
DOI:
10.1128/EC.00095-14
[Indexed for MEDLINE]
Free PMC Article
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