The Staphylococcus aureus CsoR regulates both chromosomal and plasmid-encoded copper resistance mechanisms
The Staphylococcus aureus CsoR regulates both chromosomal and plasmid-encoded copper resistance mechanisms
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DOI：
10.1111/j.1462-2920.2011.02522.x
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发表时间：
2011-09-01
影响因子：
5.1
通讯作者：
Morrissey, Julie A.
中科院分区：
文献类型：
--
作者：
Baker, Jonathan;Sengupta, Mrittika;Morrissey, Julie A.
铜是一种必需金属，在多种酶中作为辅因子发挥作用，并且是许多重要生化反应所必需的。然而，如果细胞内浓度没有得到严格调控，游离铜离子可能对细胞系统有毒性。在这项研究中，我们表明金黄色葡萄球菌对铜的抗性在每个葡萄球菌分离株中并不相同，实际上在临床菌株之间差异很大。高铜抗性被证明是由于携带一种额外的由质粒编码的铜稳态机制，即copBmco。这种质粒可以转移到对铜敏感的金黄色葡萄球菌纽曼菌株中，赋予其高铜抗性表型，这表明铜抗性有可能传播到其他金黄色葡萄球菌菌株。这是首次报道由质粒编码的铜抗性，并且表明它可以在从人类分离出的致病细菌之间转移。在金黄色葡萄球菌中鉴定出了枯草芽孢杆菌和结核分枝杆菌CsoR调节因子的同源物。金黄色葡萄球菌的csoR基因在所有已测序的金黄色葡萄球菌基因组中是保守的，并且被发现受铜诱导，并与两个下游基因一起转录：一个假定的铜伴侣蛋白（csoZ）和一个假设基因。突变和互补研究表明，与其他同源物不同，金黄色葡萄球菌CsoR在过量铜条件下对染色体和质粒编码的铜稳态机制都起负调控作用。
Copper is an essential metal which is used as a cofactor in several enzymes and is required for numerous essential biochemical reactions. However, free copper ions can be toxic to cellular systems if the intracellular concentration is not tightly regulated. In this study we show that Staphylococcus aureus copper resistance is not the same in every staphylococcal isolate, but in fact varies considerably between clinical strains. Hyper-copper-resistance was shown to be due to the carriage of an additional plasmid-encoded copper homeostasis mechanism, copBmco. This plasmid can be transferred into the copper-sensitive S. aureus Newman to confer a hyper-copper-resistant phenotype, showing that copper resistance has the potential to spread to other S. aureus strains. This is the first time that plasmid-encoded copper resistance has been reported and shown to be transferable between pathogenic bacteria isolated from humans. A homologue of the Bacillus subtilis and Mycobacterium tuberculosis CsoR regulators was identified in S. aureus. The S. aureus csoR gene is conserved in all sequenced S. aureus genomes and was found to be copper-induced and transcribed along with two downstream genes: a putative copper chaperone (csoZ) and a hypothetical gene. Mutational and complementation studies showed that unlike other homologues, the S. aureus CsoR negatively regulates both chromosomal and plasmid-encoded copper homeostasis mechanisms in response to excess-copper conditions.