Copper Stress Induces a Global Stress Response in Staphylococcus aureus and Represses sae and agr Expression and Biofilm Formation
Copper Stress Induces a Global Stress Response in Staphylococcus aureus and Represses sae and agr Expression and Biofilm Formation
复制标题
DOI：
10.1128/aem.02268-09
复制
发表时间：
2010-01-01
影响因子：
4.4
通讯作者：
Morrissey, Julie A.
中科院分区：
文献类型：
--
作者：
Baker, Jonathan;Sitthisak, Sutthirat;Morrissey, Julie A.
铜是许多酶的重要辅助因子；然而，高浓度的铜具有毒性。因此，细菌必须确保有足够的铜用作辅助因子，但更重要的是，必须限制细胞内的游离铜水平以防止毒性。在这项研究中，我们利用DNA微阵列来鉴定金黄色葡萄球菌的铜响应基因。对在过量铜环境中生长的金黄色葡萄球菌SH1000进行转录谱分析，鉴定出了一些基因，这些基因可分为四组，这表明金黄色葡萄球菌有四种主要的适应高环境铜水平的机制，如下：（i）直接铜稳态机制的诱导；（ii）氧化应激抗性的增强；（iii）错误折叠蛋白反应的表达；（iv）一些转运蛋白以及全局调控因子如Agr和Sae的抑制。我们的实验数据证实，对氧化应激的抗性，特别是对过氧化氢清除的抗性是金黄色葡萄球菌的一种重要的铜抗性机制。我们之前的研究已经表明，在低铁生长条件下，生物膜形成需要Eap和Emp蛋白，它们受到Agr和Sae的正向调控。我们的转录分析已经证实，在高铜条件下，sae、agr和eap受到抑制，并且在高铜条件下生物膜形成确实受到抑制。因此，我们的结果可能为铜膜如何防止导管上生物膜形成提供一种解释。
Copper is an important cofactor for many enzymes; however, high levels of copper are toxic. Therefore, bacteria must ensure there is sufficient copper for use as a cofactor but, more importantly, must limit free intracellular levels to prevent toxicity. In this study, we have used DNA microarray to identify Staphylococcus aureus copper-responsive genes. Transcriptional profiling of S. aureus SH1000 grown in excess copper identified a number of genes which fall into four groups, suggesting that S. aureus has four main mechanisms for adapting to high levels of environmental copper, as follows: (i) induction of direct copper homeostasis mechanisms; (ii) increased oxidative stress resistance; (iii) expression of the misfolded protein response; and (iv) repression of a number of transporters and global regulators such as Agr and Sae. Our experimental data confirm that resistance to oxidative stress and particularly to H2O2 scavenging is an important S. aureus copper resistance mechanism. Our previous studies have demonstrated that Eap and Emp proteins, which are positively regulated by Agr and Sae, are required for biofilm formation under low-iron growth conditions. Our transcriptional analysis has confirmed that sae, agr, and eap are repressed under high-copper conditions and that biofilm formation is indeed repressed under high-copper conditions. Therefore, our results may provide an explanation for how copper films can prevent biofilm formation on catheters.