AI-2-dependent gene regulation in Staphylococcus epidermidis.

AI-2-dependent gene regulation in Staphylococcus epidermidis.
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DOI:
10.1186/1471-2180-8-4
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发表时间:
2008-01-08
期刊:
影响因子:
4.2
通讯作者:
Otto, Michael
Otto, Michael
中科院分区:
生物学3区
文献类型:
--
作者:
Li, Min;Villaruz, Amer E.;Vadyvaloo, Viveka;Sturdevant, Daniel E.;Otto, Michael

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自诱导剂2 (Autoinducer 2, AI-2)是在活化的甲基循环中由luxs催化的s -核糖体同型半胱氨酸裂解反应中广泛存在的副产物,已被认为是一种种内和种间信号分子,但在许多细菌中AI-2对基因表达的控制尚不完全清楚。特别是,我们对重要的人类病原体金黄色葡萄球菌和表皮葡萄球菌中的AI-2信号传导缺乏了解。为了确定LuxS和AI-2在表皮葡萄球菌中的作用,我们分析了表皮葡萄球菌LuxS突变体和添加过表达的表皮葡萄球菌Pfs和LuxS酶合成的AI-2后基因表达的全基因组变化。AI-2控制的基因主要包括糖、核苷酸、氨基酸和氮代谢相关基因,以及编码脂肪酶和细菌凋亡蛋白的毒力相关基因。此外,我们通过培养滤液的液相色谱/质谱分析证明,促炎酚溶性调节素(PSM)肽是表皮葡萄球菌的关键毒力因子,在luxS/AI-2的控制下。我们的研究结果为LuxS在表皮葡萄球菌毒力中的作用提供了详细的分子基础,并提示AI-2在表皮葡萄球菌中具有信号功能。
Autoinducer 2 (AI-2), a widespread by-product of the LuxS-catalyzed S-ribosylhomocysteine cleavage reaction in the activated methyl cycle, has been suggested to serve as an intra- and interspecies signaling molecule, but in many bacteria AI-2 control of gene expression is not completely understood. Particularly, we have a lack of knowledge about AI-2 signaling in the important human pathogens Staphylococcus aureus and S. epidermidis. To determine the role of LuxS and AI-2 in S. epidermidis, we analyzed genome-wide changes in gene expression in an S. epidermidis luxS mutant and after addition of AI-2 synthesized by over-expressed S. epidermidis Pfs and LuxS enzymes. Genes under AI-2 control included mostly genes involved in sugar, nucleotide, amino acid, and nitrogen metabolism, but also virulence-associated genes coding for lipase and bacterial apoptosis proteins. In addition, we demonstrate by liquid chromatography/mass-spectrometry of culture filtrates that the pro-inflammatory phenol-soluble modulin (PSM) peptides, key virulence factors of S. epidermidis, are under luxS/AI-2 control. Our results provide a detailed molecular basis for the role of LuxS in S. epidermidis virulence and suggest a signaling function for AI-2 in this bacterium.
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