The Yin and Yang of copper during infection.
The Yin and Yang of copper during infection.
复制标题
感染过程中铜的阴阳和阳。
DOI：
10.1007/s00775-016-1335-1
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Culotta VC
中科院分区：
文献类型：
--
作者：
Besold AN;Culbertson EM;Culotta VC
铜对于病原体和它们感染的动物宿主来说都是一种必不可少的微量营养素。然而，铜也可能对细胞有毒，因为它的氧化还原特性和破坏金属蛋白的活性部位的能力，如铁-S酶。通过这些有毒的特性，铜是一种有效的抗菌剂，天然免疫中的一个新兴概念是动物宿主故意利用抗菌武器中的铜毒性。特别是，巨噬细胞可以攻击高铜入侵的微生物，这种金属在肺部感染的部位也会升高。此外，在感染多种病原体的过程中，血清中的铜水平也会升高。为了防御这种有毒的铜，微生物入侵者配备了一系列铜解毒防御系统，以促进宿主的生存，包括铜出口ATPase和铜结合金属硫蛋白。然而，重要的是要记住，铜也是微生物病原体的基本营养物质，是呼吸作用的细胞色素C氧化酶、抗氧化防御的超氧化物歧化酶以及作用于金属和有机底物的多铜氧化酶等酶的重要辅因子。因此，我们假设动物宿主也可以通过限制其铜营养来阻止病原体的生长，类似于已有文献证明的锌、锰和铁等微量营养素对饥饿微生物的营养免疫效果。这篇综述提供了铜故事的两个方面，并评估了宿主如何在宿主-病原体战场上利用铜的毒素或铜的营养在抗菌策略中发挥作用。
Copper is an essential micronutrient for both pathogens and the animal hosts they infect. However, copper can also be toxic in cells due to its redox properties and ability to disrupt active sites of metalloproteins, such as Fe-S enzymes. Through these toxic properties, copper is an effective antimicrobial agent and an emerging concept in innate immunity is that the animal host intentionally exploits copper toxicity in antimicrobial weaponry. In particular, macrophages can attack invading microbes with high copper and this metal is also elevated at sites of lung infection. In addition, copper levels in serum rise during infection with a wide array of pathogens. To defend against this toxic copper, the microbial intruder is equipped with a battery of copper detoxification defenses that promote survival in the host, including copper exporting ATPases and copper binding metallothioneins. However, it is important to remember that copper is also an essential nutrient for microbial pathogens and serves as important cofactor for enzymes such as cytochrome c oxidase for respiration, superoxide dismutase for anti-oxidant defense and multi-copper oxidases that act on metals and organic substrates. We therefore posit that the animal host can also thwart pathogen growth by limiting their copper nutrients, similar to the well-documented nutritional immunity effects for starving microbes of essential zinc, manganese and iron micronutrients. This review provides both sides of the copper story and evaluates how the host can exploit either copper-the-toxin or copper-the-nutrient in antimicrobial tactics at the host-pathogen battleground.
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