Copper microenvironments in the human body define patterns of copper adaptation in pathogenic bacteria.
Copper microenvironments in the human body define patterns of copper adaptation in pathogenic bacteria.
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DOI：
10.1371/journal.ppat.1010617
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发表时间：
2022-07
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
铜是大多数生物体必需的微量营养素，是原核生物和真核生物所编码的关键铜依赖性酶的辅助因子。几十年来积累的证据表明，铜在哺乳动物免疫系统的功能中发挥着重要作用。铜在感染部位积累，包括胃肠道和呼吸道以及血液和尿液中，吞噬细胞直接利用其抗菌毒性来杀死病原体。缺铜的动物更容易受到感染，而喂食富含铜的食物的动物则更具抵抗力。因此，铜抗性基因是细菌病原体的重要毒力因子，使它们能够在对铜的侵害进行解毒的同时，维持其必需的铜酶的铜供应。在此，我们描述了铜在哺乳动物对感染的反应中所起的各种作用的累积证据，表明这种金属对免疫功能有许多直接和间接的影响。我们进一步阐述了病原菌在入侵宿主时对升高的铜浓度的多方面反应，描述了对铜毒性的保守性和物种特异性适应。总之，这些观察结果证明了铜在宿主 - 病原体界面的作用，并说明了为什么细菌的铜解毒系统可以成为未来新型抗生素药物开发计划的可行靶点。
铜作为微量营养素，动物和细菌都需要少量的铜。在感染期间，哺乳动物免疫系统会提高局部铜浓度，这会导致病原体中的铜毒性。反过来，细菌病原体拥有专门的系统来抵抗这种铜毒性。铜在免疫系统的功能中也起着重要的间接作用。在这篇综述中，我们解释了铜在人体内的多种作用，重点是其在免疫系统中的功能。我们还描述了细菌病原体在感染期间如何应对在宿主体内所经历的铜毒性，阐述了细菌中保守的铜稳态和解毒系统以及已被证明对致病性很重要的物种特异性适应。铜在宿主 - 病原体界面的关键作用以及病原菌抵抗铜毒性的基本需求，使得赋予病原体抗性的蛋白质成分成为未来开发新型抗生素药物的潜在靶点。
Copper is an essential micronutrient for most organisms that is required as a cofactor for crucial copper-dependent enzymes encoded by both prokaryotes and eukaryotes. Evidence accumulated over several decades has shown that copper plays important roles in the function of the mammalian immune system. Copper accumulates at sites of infection, including the gastrointestinal and respiratory tracts and in blood and urine, and its antibacterial toxicity is directly leveraged by phagocytic cells to kill pathogens. Copper-deficient animals are more susceptible to infection, whereas those fed copper-rich diets are more resistant. As a result, copper resistance genes are important virulence factors for bacterial pathogens, enabling them to detoxify the copper insult while maintaining copper supply to their essential cuproenzymes. Here, we describe the accumulated evidence for the varied roles of copper in the mammalian response to infections, demonstrating that this metal has numerous direct and indirect effects on immune function. We further illustrate the multifaceted response of pathogenic bacteria to the elevated copper concentrations that they experience when invading the host, describing both conserved and species-specific adaptations to copper toxicity. Together, these observations demonstrate the roles of copper at the host–pathogen interface and illustrate why bacterial copper detoxification systems can be viable targets for the future development of novel antibiotic drug development programs. Copper is required by both animals and bacteria in small quantities as a micronutrient. During infection, the mammalian immune system increases the local concentration of copper, which gives rise to copper toxicity in the pathogen. In turn, bacterial pathogens possess specialized systems to resist this copper toxicity. Copper also plays important, indirect roles in the function of the immune system. In this review, we explain the diverse roles of copper in the human body with a focus on its functions within the immune system. We also describe how bacterial pathogens respond to the copper toxicity that they experience within the host during infection, illustrating both conserved copper homeostasis and detoxification systems in bacteria and species-specific adaptations that have been shown to be important to pathogenicity. The key role of copper at the host–pathogen interface and the essential requirement for pathogenic bacteria to resist copper toxicity makes the protein components that confer resistance on pathogens potential targets for future development of novel antibiotic drugs.
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影响因子：
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