Copper intoxication inhibits aerobic nucleotide synthesis in Streptococcus pneumoniae

Michael D.L. Johnson, Thomas E. Kehl-Fie, Jason W. Rosch

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Copper is universally toxic in excess, a feature exploited by the human immune system to facilitate bacterial clearance. The mechanism of copper intoxication remains unknown for many bacterial species. Here, we demonstrate that copper toxicity in Streptococcus pneumoniae is independent from oxidative stress but, rather, is the result of copper inhibiting the aerobic dNTP biosynthetic pathway. Furthermore, we show that copper-intoxicated S. pneumoniae is rescued by manganese, which is an essential metal in the aerobic nucleotide synthesis pathway. These data provide insight into new targets to enhance copper-mediated toxicity during bacterial clearance.

Original languageEnglish (US)
Pages (from-to)786-794
Number of pages9
JournalMetallomics
Volume7
Issue number5
DOIs
StatePublished - May 1 2015
Externally publishedYes

Fingerprint

Nucleotides
Streptococcus pneumoniae
Copper
Toxicity
Oxidative stress
Immune system
Poisons
Biosynthetic Pathways
Manganese
Immune System
Oxidative Stress
Metals

ASJC Scopus subject areas

  • Chemistry (miscellaneous)
  • Biophysics
  • Biomaterials
  • Biochemistry
  • Metals and Alloys

Cite this

Copper intoxication inhibits aerobic nucleotide synthesis in Streptococcus pneumoniae. / Johnson, Michael D.L.; Kehl-Fie, Thomas E.; Rosch, Jason W.

In: Metallomics, Vol. 7, No. 5, 01.05.2015, p. 786-794.

Research output: Contribution to journalArticle

Johnson, Michael D.L. ; Kehl-Fie, Thomas E. ; Rosch, Jason W. / Copper intoxication inhibits aerobic nucleotide synthesis in Streptococcus pneumoniae. In: Metallomics. 2015 ; Vol. 7, No. 5. pp. 786-794.
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