Strength of Cu-efflux response in Escherichia coli coordinates metal resistance in Caenorhabditis elegans and contributes to the severity of environmental toxicity.
Strength of Cu-efflux response in Escherichia coli coordinates metal resistance in Caenorhabditis elegans and contributes to the severity of environmental toxicity.
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DOI：
10.1016/j.jbc.2021.101060
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
McEvoy MM
中科院分区：
文献类型：
--
作者：
Shafer CM;Tseng A;Allard P;McEvoy MM
如果没有有效的体内平衡系统，过量的铜 (Cu) 对生物体普遍有毒。虽然环境中人为铜的利用增加推动了肠细菌内铜抗性系统的多样化，但很少有研究关注细菌结构的这种变化如何影响需要维持自身铜稳态的宿主生物体。因此，我们利用简化的宿主-微生物系统来确定一种细菌铜抗性系统的效率，通过普遍存在的 CusRS 双组分系统增加铜的流出能力，是否有助于宿主秀丽隐杆线虫中铜的可用性和随后的毒性。我们发现，细菌中功能齐全的铜流出系统增加了宿主线虫中铜毒性的严重程度，而不会增加秀丽隐杆线虫的铜体负担。相反，宿主体内铜毒性的增加与线虫后咽中保护性金属应激反应基因 numr-1 表达的减少有关，在该基因中，咽部研磨会分解摄入的细菌，然后再进入消化道。 numr-1 转基因激活的空间定位和线虫中细菌依赖性铜抗性的丧失，而没有有效的 numr-1 反应，支持了 numr-1 对细菌铜流出能力有反应的假设。我们认为细菌的铜流出能力是宿主对慢性铜应激反应的一个强有力的空间决定因素。
Without effective homeostatic systems in place, excess copper (Cu) is universally toxic to organisms. While increased utilization of anthropogenic Cu in the environment has driven the diversification of Cu-resistance systems within enterobacteria, little research has focused on how this change in bacterial architecture impacts host organisms that need to maintain their own Cu homeostasis. Therefore, we utilized a simplified host–microbe system to determine whether the efficiency of one bacterial Cu-resistance system, increasing Cu-efflux capacity via the ubiquitous CusRS two-component system, contributes to the availability and subsequent toxicity of Cu in host Caenorhabditis elegans nematode. We found that a fully functional Cu-efflux system in bacteria increased the severity of Cu toxicity in host nematodes without increasing the C. elegans Cu-body burden. Instead, increased Cu toxicity in the host was associated with reduced expression of a protective metal stress-response gene, numr-1, in the posterior pharynx of nematodes where pharyngeal grinding breaks apart ingested bacteria before passing into the digestive tract. The spatial localization of numr-1 transgene activation and loss of bacterially dependent Cu-resistance in nematodes without an effective numr-1 response support the hypothesis that numr-1 is responsive to the bacterial Cu-efflux capacity. We propose that the bacterial Cu-efflux capacity acts as a robust spatial determinant for a host’s response to chronic Cu stress.
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影响因子：
3.6
作者：
BROWN, NL;BARRETT, SR;ROUCH, DA
通讯作者：
ROUCH, DA
DOI：
10.1073/pnas.1517448112
发表时间：
2015-10-06
影响因子：
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影响因子：
1.6
作者：
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通讯作者：
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影响因子：
4.8
作者：
Chun, Haarin;Sharma, Anuj Kumar;Kim, Byung-Eun
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