Pohl Konstanze, Francois Patrice, Stenz Ludwig, Schlink Frank, Geiger Tobias, Herbert Silvia, Goerke Christiane, Schrenzel Jacques, Wolz Christiane
Institute of Medical Microbiology and Hygiene, University of Tübingen, [corrected] Tübingen, Germany.
J Bacteriol. 2009 May;191(9):2953-63. doi: 10.1128/JB.01492-08. Epub 2009 Feb 27.
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.
据报道，阻遏蛋白CodY可抑制主要参与氮代谢的代谢基因。我们分析了来自三株不相关金黄色葡萄球菌菌株（Newman、UAMS-1和RN1HG）的codY突变体。在化学成分确定的培养基中，这些突变体的生长速度比其亲本菌株慢。然而，只有codY突变体能够在缺乏苏氨酸的培养基中生长。过量的异亮氨酸会导致野生型生长受抑制，但对codY突变体无此影响，这表明异亮氨酸在CodY依赖性阻遏中发挥作用。包括毒力调节因子agr在内的典型CodY抑制基因在添加异亮氨酸后上调时受到抑制。CodY对agr的依赖性抑制与CodY对典型agr调节基因如cap、spa、fnbA和coa的伴随影响一致。然而，其中一些毒力基因（如cap、fnbA和spa）在agr阴性背景下也受CodY调控。微阵列分析显示，绝大多数CodY抑制基因参与氨基酸代谢；CodY激活的基因主要参与核苷酸代谢或毒力。总之，金黄色葡萄球菌中的CodY不仅作为参与氮代谢的基因的阻遏物，还通过支持以及替代agr功能来促进毒力基因的调控。
