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Copper potentiates azole antifungal activity in a way that does not involve complex formation.

Publication ,  Journal Article
Hunsaker, EW; Franz, KJ
Published in: Dalton transactions (Cambridge, England : 2003)
July 2019

To survive, fungal pathogens must acquire nutrient metals that are restricted by the host while also tolerating mechanisms of metal toxicity that are induced by the host. Given this dual vulnerability, we hypothesized that a pathogen's access to and control of essential yet potentially dangerous metal ions would affect fungal tolerance to antifungal drug stress. Here, we show that Candida albicans becomes sensitized to both Cu limitation and Cu elevation during exposure in liquid culture to the antifungal drug fluconazole, a widely prescribed antifungal agent. Spectroscopic data confirm that while fluconazole forms a complex with Cu(ii) in water, interactions of fluconazole with neither Cu(ii) nor Cu(i) are observed in the cell culture media used for the cellular assays. This result is further supported by growth assays in deletion strains that lack Cu import machinery. Overall, we establish that increases in Cu levels by as little as 40 nM over basal levels in the growth medium reduce tolerance of C. albicans to fluconazole in a way that does not require formation of a Cu-fluconazole complex. Rather, our data point to a more complex relationship between drug stress and Cu availability that gives rise to metal-mediated outcomes of drug treatment.

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Published In

Dalton transactions (Cambridge, England : 2003)

DOI

EISSN

1477-9234

ISSN

1477-9226

Publication Date

July 2019

Volume

48

Issue

26

Start / End Page

9654 / 9662

Related Subject Headings

  • Inorganic & Nuclear Chemistry
  • 3402 Inorganic chemistry
  • 0399 Other Chemical Sciences
  • 0307 Theoretical and Computational Chemistry
  • 0302 Inorganic Chemistry
 

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Hunsaker, E. W., & Franz, K. J. (2019). Copper potentiates azole antifungal activity in a way that does not involve complex formation. Dalton Transactions (Cambridge, England : 2003), 48(26), 9654–9662. https://doi.org/10.1039/c9dt00642g
Hunsaker, Elizabeth W., and Katherine J. Franz. “Copper potentiates azole antifungal activity in a way that does not involve complex formation.Dalton Transactions (Cambridge, England : 2003) 48, no. 26 (July 2019): 9654–62. https://doi.org/10.1039/c9dt00642g.
Hunsaker EW, Franz KJ. Copper potentiates azole antifungal activity in a way that does not involve complex formation. Dalton transactions (Cambridge, England : 2003). 2019 Jul;48(26):9654–62.
Hunsaker, Elizabeth W., and Katherine J. Franz. “Copper potentiates azole antifungal activity in a way that does not involve complex formation.Dalton Transactions (Cambridge, England : 2003), vol. 48, no. 26, July 2019, pp. 9654–62. Epmc, doi:10.1039/c9dt00642g.
Hunsaker EW, Franz KJ. Copper potentiates azole antifungal activity in a way that does not involve complex formation. Dalton transactions (Cambridge, England : 2003). 2019 Jul;48(26):9654–9662.
Journal cover image

Published In

Dalton transactions (Cambridge, England : 2003)

DOI

EISSN

1477-9234

ISSN

1477-9226

Publication Date

July 2019

Volume

48

Issue

26

Start / End Page

9654 / 9662

Related Subject Headings

  • Inorganic & Nuclear Chemistry
  • 3402 Inorganic chemistry
  • 0399 Other Chemical Sciences
  • 0307 Theoretical and Computational Chemistry
  • 0302 Inorganic Chemistry