Copper intoxication inhibits aerobic nucleotide synthesis in Streptococcus pneumoniae

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 oxidativ...

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Bibliographic Details
Published inMetallomics Vol. 7; no. 5; p. 786
Main Authors Johnson, Michael D L, Kehl-Fie, Thomas E, Rosch, Jason W
Format Journal Article
LanguageEnglish
Published England 01.05.2015
Subjects
Animals
Biosynthetic Pathways
Cell Line
Copper - metabolism
Gene Expression Regulation, Bacterial
Humans
Macrophages - metabolism
Macrophages - microbiology
Manganese - metabolism
Mice
Nucleotides - metabolism
Oxidative Stress
Pneumococcal Infections - metabolism
Pneumococcal Infections - microbiology
Streptococcus pneumoniae - genetics
Streptococcus pneumoniae - growth & development
Streptococcus pneumoniae - metabolism
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Summary: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.
ISSN:1756-591X
DOI:10.1039/c5mt00011d