Copper stress in Staphylococcus aureus leads to adaptive changes in central carbon metabolism
Copper stress in Staphylococcus aureus leads to adaptive changes in central carbon metabolism
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DOI：
10.1039/c8mt00239h
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发表时间：
2019-01-01
期刊：
影响因子：
3.4
通讯作者：
Waldron, Kevin J.
中科院分区：
文献类型：
--
作者：
Tarrant, Emma;Riboldi, Gustavo P.;Waldron, Kevin J.
铜毒性一直是细菌的长期选择压力，因为它存在于环境中，并且通过放牧原生动物、免疫系统的吞噬细胞以及人造医疗和商业产品用作抗菌剂。最近有证据表明，暴露于增加的铜胁迫可能是耐甲氧西林金黄色葡萄球菌进化和传播的关键驱动因素，这是一种全球重要的病原体，在全世界范围内导致显着的死亡率和发病率。然而，目前尚不清楚金黄色葡萄球菌的生理机能如何受到铜胁迫的影响，或者它如何适应以便能够在过量铜的存在下生长。在这里，我们定量确定了金黄色葡萄球菌在铜胁迫条件下生长过程中如何改变其蛋白质组，比较了两种不同类型的生长模式中的这种适应性反应。我们发现适应性反应涉及保守的铜解毒系统的诱导以及中心碳代谢酶的诱导，而仅有限地诱导参与氧化应激反应的蛋白质。此外，我们还发现了一种在铜过量的压力下与金黄色葡萄球菌细胞内的铜结合的蛋白质。这种铜结合酶是糖酵解所必需的甘油醛-3-磷酸脱氢酶，在体外和金黄色葡萄球菌细胞内都会被铜抑制。总之，我们的数据表明，铜应激导致金黄色葡萄球菌糖酵解受到抑制，并且细菌通过改变其中心碳利用途径来适应这种应激。
Copper toxicity has been a long-term selection pressure on bacteria due to its presence in the environment and its use as an antimicrobial agent by grazing protozoa, by phagocytic cells of the immune system, and in man-made medical and commercial products. There is recent evidence that exposure to increased copper stress may have been a key driver in the evolution and spread of methicillin-resistant Staphylococcus aureus, a globally important pathogen that causes significant mortality and morbidity worldwide. Yet it is unclear how S. aureus physiology is affected by copper stress or how it adapts in order to be able to grow in the presence of excess copper. Here, we have determined quantitatively how S. aureus alters its proteome during growth under copper stress conditions, comparing this adaptive response in two different types of growth regime. We found that the adaptive response involves induction of the conserved copper detoxification system as well as induction of enzymes of central carbon metabolism, with only limited induction of proteins involved in the oxidative stress response. Further, we identified a protein that binds copper inside S. aureus cells when stressed by copper excess. This copper-binding enzyme, a glyceraldehyde-3-phosphate dehydrogenase essential for glycolysis, is inhibited by copper in vitro and inside S. aureus cells. Together, our data demonstrate that copper stress leads to the inhibition of glycolysis in S. aureus, and that the bacterium adapts to this stress by altering its central carbon utilisation pathways.