Histatin-5 interacts with cellular copper to promote antifungal activity against Candida albicans

Abstract Histatin-5 (Hist-5) is an antimicrobial peptide found in human saliva that functions to defend the oral cavity from microbial infections, such as those caused by the fungal pathogen Candida albicans (C. albicans). Hist-5 can bind Cu in multiple oxidation states, Cu2+ and Cu+  in vitro, and...

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Veröffentlicht in:Metallomics 2023-12, Vol.15 (12)
Hauptverfasser: Campbell, Joanna X, Schulte, Natalie B, Lai, Barry, Harris, Hugh H, Franz, Katherine J
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Sprache:eng
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Zusammenfassung:Abstract Histatin-5 (Hist-5) is an antimicrobial peptide found in human saliva that functions to defend the oral cavity from microbial infections, such as those caused by the fungal pathogen Candida albicans (C. albicans). Hist-5 can bind Cu in multiple oxidation states, Cu2+ and Cu+  in vitro, and supplemental Cu2+ has been shown to improve the fungicidal activity of the peptide against C. albicans in culture. However, the exact role of Cu on the antifungal activity of Hist-5 and whether direct peptide–Cu interactions occur intracellularly has yet to be fully determined. Here, we used a combination of fluorescence spectroscopy and confocal microscopy experiments to show reversible Cu-dependent quenching of a fluorescent Hist-5 analogue, Hist-5*, indicating a direct interaction between Hist-5 and intracellular Cu. X-ray fluorescence microscopy images revealed peptide-induced changes to cellular Cu distribution and cell-associated Cu content. These data support a model in which Hist-5 can facilitate the hyperaccumulation of Cu in C. albicans and directly interact with Cu intracellularly to increase the fungicidal activity of Hist-5. Graphical Abstract Graphical Abstract Histatin-5 facilitates Cu hyperaccumulation, localization, and cidality in Candida albicans.
ISSN:1756-591X
1756-5901
1756-591X
DOI:10.1093/mtomcs/mfad070