Interaction of Copper Toxicity and Oxidative Stress in Campylobacter jejuni
Interaction of Copper Toxicity and Oxidative Stress in Campylobacter jejuni
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DOI：
10.1128/jb.00208-18
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发表时间：
2018-11-01
影响因子：
3.2
通讯作者：
Olson, Jonathan W.
中科院分区：
文献类型：
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作者：
Gardner, Susan P.;Olson, Jonathan W.
铜既是大多数生物体（包括空肠弯曲菌）所需的微量营养素，也是毒性来源。空肠弯曲菌中表达的两种蛋白质（称为 CopA 和 CueO）已被证明分别是铜转运蛋白和多铜氧化酶。我们分离出了这些基因发生突变的菌株，在这里我们报告说，它们更容易受到生长培养基中铜的添加和诱导的氧化应激的影响。两种突变株在鸟类宿主中的定植都有缺陷，饲料中的铜加剧了定植缺陷。与非表达菌株或表达肽的非铜结合版本的菌株相比，源自 CueO 的正常周质铜结合区域的细胞质肽的过度表达也引起铜不耐受。综上所述，结果表明，空肠弯曲菌中的铜毒性是由于未能有效隔离细胞质铜，导致铜介导的氧化损伤增加。 重要性 铜是大多数需氧生物体所需的微量营养素，但在高浓度下普遍有毒。这些生物体利用稳态机制，使细胞能够获得足够的元素来维持代谢需求，同时确保细胞内不会积累致死水平。空肠弯曲杆菌是一种重要的食源性病原体，通常通过受污染的家禽进入食物链。空肠弯曲杆菌对铜有代谢需求，并编码铜解毒系统。在研究这个系统的过程中，我们了解到它对于鸟类的殖民很重要。我们还深入了解了铜如何通过促进氧化应激在空肠弯曲菌中发挥毒性作用。
Copper is both a required micronutrient and a source of toxicity in most organisms, including Campylobacter jejuni. Two proteins expressed in C. jejuni (termed CopA and CueO) have been shown to be a copper transporter and multicopper oxidase, respectively. We have isolated strains with mutations in these genes, and here we report that they were more susceptible to both the addition of copper in the growth media and to induced oxidative stress. Both mutant strains were defective in colonization of an avian host, and copper in the feed exacerbated the colonization deficiency. Overexpression of a cytoplasmic peptide derived from the normally periplasmic copper-binding region of CueO also caused copper intolerance compared to nonexpressing strains or strains expressing the non-copper-binding versions of the peptide. Taken together, the results indicate that copper toxicity in C. jejuni is due to a failure to effectively sequester cytoplasmic copper, resulting in an increase in copper-mediated oxidative damage.IMPORTANCE Copper is a required micronutrient for most aerobic organisms, but it is universally toxic at elevated levels. These organisms use homeostatic mechanisms that allow for cells to acquire enough of the element to sustain metabolic requirements while ensuring that lethal levels cannot build up in the cell. Campylobacter jejuni is an important foodborne pathogen that typically makes its way into the food chain through contaminated poultry. C. jejuni has a metabolic requirement for copper and encodes a copper detoxification system. In the course of studying this system, we have learned that it is important for avian colonization. We have also gained insight into how copper exerts its toxic effects in C. jejuni by promoting oxidative stress.