Copper intoxication inhibits aerobic nucleotide synthesis in Streptococcus pneumoniae
Copper intoxication inhibits aerobic nucleotide synthesis in Streptococcus pneumoniae
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DOI：
10.1039/c5mt00011d
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发表时间：
2015-01-01
期刊：
影响因子：
3.4
通讯作者：
Rosch, Jason W.
中科院分区：
文献类型：
--
作者：
Johnson, Michael D. L.;Kehl-Fie, Thomas E.;Rosch, Jason W.
过量的铜是普遍有毒的，人体免疫系统利用这一特性来促进细菌的清除。许多细菌种类的铜中毒机制尚不清楚。在这里，我们证明了铜对肺炎链球菌的毒性与氧化应激无关，而是铜抑制有氧dNTP生物合成途径的结果。此外，我们发现铜中毒肺炎链球菌被锰拯救，锰是有氧核苷酸合成途径中必需的金属。这些数据为在细菌清除过程中增强铜介导的毒性提供了新的靶点。
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.