Specific Histidine Residues Confer Histatin Peptides with Copper-Dependent Activity against Candida albicans.

ABSTRACT: The histidine-rich salivary peptides of the histatin family are known to bind copper (Cu) and other metal ions in vitro; however, the details of these interactions are poorly understood, and their implications for in vivo antifungal activity have not been established. Here, we show that the availability of Cu during exposure of Candida albicans to histatin-5 (Hist-5) modulates its antifungal activity. Antifungal susceptibility testing revealed that co-treatment of Hist-5 with Cu improved the EC₅₀ from ∼5 to ∼1 μM, whereas co-treatment with a high-affinity Cu-specific chelator abrogated antifungal activity. Spectrophotometric titrations revealed two previously unrecognized Cu(I)-binding sites with apparent K_d values at pH 7.4, ∼20 nM, and confirmed a high-affinity Cu(I

SUBMITTER: Conklin SE 

PROVIDER: S-EPMC5937946 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature