CodY in Staphylococcus aureus: a Regulatory Link between Metabolism and Virulence Gene Expression
CodY in Staphylococcus aureus: a Regulatory Link between Metabolism and Virulence Gene Expression
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DOI：
10.1128/jb.01492-08
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发表时间：
2009-05-01
影响因子：
3.2
通讯作者：
Wolz, Christiane
中科院分区：
文献类型：
--
作者：
Pohl, Konstanze;Francois, Patrice;Wolz, Christiane
据报道，阻遏物CodY抑制主要参与氮代谢的代谢基因。我们分析了来自三种无关金黄色葡萄球菌菌株（纽曼、UAMS-1和RN 1HG）的codY突变体。在化学成分确定的培养基中，突变株的生长速度比它们的亲本菌株慢。然而，只有codY突变体能够在缺乏苏氨酸的培养基中生长。过量的异亮氨酸导致在野生型中的生长抑制，但不是在codY突变体中，这表明异亮氨酸在CodY依赖性阻遏中起作用。原型CodY抑制基因，包括毒力调节agr的抑制后上调异亮氨酸。CodY依赖的agr抑制与CodY对典型agr调节基因如cap、spa、fnbA和coa的伴随影响一致。然而，这些毒力基因中的一些（例如，cap、fnbA和spa）在agr阴性背景下也受CodY调控。基因芯片分析表明，CodY抑制基因主要参与氨基酸代谢，CodY激活基因主要参与核苷酸代谢或毒力。综上所述，S.金黄色葡萄球菌不仅作为参与氮代谢的基因的阻遏物，而且通过支持以及取代AGR功能而有助于毒力基因调节。
The repressor CodY is reported to inhibit metabolic genes mainly involved in nitrogen metabolism. We analyzed codY mutants from three unrelated Staphylococcus aureus strains (Newman, UAMS-1, and RN1HG). The mutants grew more slowly than their parent strains in a chemically defined medium. However, only codY mutants were able to grow in medium lacking threonine. An excess of isoleucine resulted in growth inhibition in the wild type but not in the codY mutants, indicating that isoleucine plays a role in CodY-dependent repression. Prototypic CodY-repressed genes including the virulence regulator agr are repressed after up-shift with isoleucine. The CodY-dependent repression of agr is consistent with the concomitant influence of CodY on typical agr-regulated genes such as cap, spa, fnbA, and coa. However, some of these virulence genes (e.g., cap, fnbA, and spa) were also regulated by CodY in an agr-negative background. Microarray analysis revealed that the large majority of CodY-repressed genes were involved in amino acid metabolism; CodY-activated genes were mainly involved in nucleotide metabolism or virulence. In summary, CodY in S. aureus not only acts as a repressor for genes involved in nitrogen metabolism but also contributes to virulence gene regulation by supporting as well as substituting for agr function.