Chemical and functional properties of metal chelators that mobilize copper to elicit fungal killing of Cryptococcus neoformans.

Journal Article

A panel of iron (Fe) and copper (Cu) chelators was screened for growth inhibitory activity against the fungal pathogen Cryptococcus neoformans. Select bidentate metal-binding ligands containing mixed O,S or O,N donor atoms were identified as agents that induce cell killing in a Cu-dependent manner. Conversely, structurally similar ligands with O,O donor atoms did not inhibit C. neoformans growth regardless of Cu status. Studies of Cu(ii) and Cu(i) binding affinity, lipophilicity, and growth recovery assays of Cu-import deficient cells identified lipophilicity of thermodynamically stable CuIIL2 complexes as the best predictor of antifungal activity. These same complexes induce cellular hyperaccumulation of Zn and Fe in addition to Cu. The results described here present the utility of appropriate metal-binding ligands as potential antifungal agents that manipulate cellular metal balance as an antimicrobial strategy.

Full Text

Duke Authors

Cited Authors

  • Helsel, ME; White, EJ; Razvi, SZA; Alies, B; Franz, KJ

Published Date

  • January 2017

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 69 - 81

PubMed ID

  • 27853789

Electronic International Standard Serial Number (EISSN)

  • 1756-591X

International Standard Serial Number (ISSN)

  • 1756-5901

Digital Object Identifier (DOI)

  • 10.1039/c6mt00172f

Language

  • eng