Role of Copper Efflux in Pneumococcal Pathogenesis and Resistance to Macrophage-Mediated Immune Clearance
Role of Copper Efflux in Pneumococcal Pathogenesis and Resistance to Macrophage-Mediated Immune Clearance
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DOI：
10.1128/iai.03015-14
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发表时间：
2015-04-01
影响因子：
3.1
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.
在细菌中，金属的细胞内水平是由严格控制的获取和流出系统介导的。对于铜来说尤其如此，铜是一种普遍有毒的微量元素。在感染过程中，哺乳动物宿主利用铜的毒性来促进细菌清除。为了更好地了解铜在感染过程中的作用，我们描述了 cop 操纵子对肺炎链球菌铜稳态和毒力的贡献。删除由 copA 编码的输出蛋白或由 cupA 编码的伴侣蛋白，都会导致对铜应激的超敏反应。我们进一步证明，copA 编码的铜输出蛋白的缺失导致肺部、腹膜内和静脉内感染模型的毒力降低。 copA 的缺失导致巨噬细胞介导的体外细菌清除增强。人们发现肺部copA突变体的减毒表型依赖于肺巨噬细胞，这强调了铜外流在逃避免疫防御中的重要性。总的来说，这些数据深入了解了 cop 操纵子在肺炎球菌发病机制中的作用。
In bacteria, the intracellular levels of metals are mediated by tightly controlled acquisition and efflux systems. This is particularly true of copper, a trace element that is universally toxic in excess. During infection, the toxic properties of copper are exploited by the mammalian host to facilitate bacterial clearance. To better understand the role of copper during infection, we characterized the contribution of the cop operon to copper homeostasis and virulence in Streptococcus pneumoniae. Deletion of either the exporter, encoded by copA, or the chaperone, encoded by cupA, led to hypersensitivity to copper stress. We further demonstrated that loss of the copper exporter encoded by copA led to decreased virulence in pulmonary, intraperitoneal, and intravenous models of infection. Deletion of copA resulted in enhanced macrophage-mediated bacterial clearance in vitro. The attenuation phenotype of the copA mutant in the lung was found to be dependent on pulmonary macrophages, underscoring the importance of copper efflux in evading immune defenses. Overall, these data provide insight into the role of the cop operon in pneumococcal pathogenesis.