Tricarboxylic Acid Cycle-Dependent Regulation of Staphylococcus epidermidis Polysaccharide Intercellular Adhesin Synthesis
Tricarboxylic Acid Cycle-Dependent Regulation of Staphylococcus epidermidis Polysaccharide Intercellular Adhesin Synthesis
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DOI：
10.1128/jb.00806-08
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发表时间：
2008-12-01
影响因子：
3.2
通讯作者：
Somerville, Greg A.
中科院分区：
文献类型：
--
作者：
Sadykov, Marat R.;Olson, Michael E.;Somerville, Greg A.
表皮葡萄球菌是一种主要的医院病原体，主要感染免疫功能低下的个体或植入生物材料的个体（例如，例如，在一个实施例中，导管）。生物材料相关感染通常涉及在医疗器械表面上形成生物膜。In S.多糖细胞间粘附素（PIA）是表皮生物膜形成和发病的重要介质。PIA的合成受至少三种DNA结合蛋白（IcaR、SarA和sigma（B））以及若干环境和营养条件调节。以前，我们观察到的环境条件，增加PIA合成减少三羧酸（TCA）循环活动。在本研究中，S.构建了epidermidis TCA循环突变体，并对PIA生物合成中的中心代谢功能进行了研究。TCA循环失活改变了S.表皮生长因子抑制PIA生物合成基因的表达，导致PIA生物合成基因的大量去阻遏，并将生长中的碳重定向到PIA生物合成中。这些数据表明，细菌代谢状态是PIA合成的关键调控决定因素。此外，这些数据使我们提出，TCA循环作为一种信号转导途径，将外部环境线索转化为细胞内代谢信号，调节转录调节因子的活性。
Staphylococcus epidermidis is a major nosocomial pathogen primarily infecting immunocompromised individuals or those with implanted biomaterials (e. g., catheters). Biomaterial-associated infections often involve the formation of a biofilm on the surface of the medical device. In S. epidermidis, polysaccharide intercellular adhesin (PIA) is an important mediator of biofilm formation and pathogenesis. Synthesis of PIA is regulated by at least three DNA binding proteins (IcaR, SarA, and sigma(B)) and several environmental and nutritional conditions. Previously, we observed the environmental conditions that increased PIA synthesis decreased tricarboxylic acid (TCA) cycle activity. In this study, S. epidermidis TCA cycle mutants were constructed, and the function of central metabolism in PIA biosynthesis was examined. TCA cycle inactivation altered the metabolic status of S. epidermidis, resulting in a massive derepression of PIA biosynthetic genes and a redirection of carbon from growth into PIA biosynthesis. These data demonstrate that the bacterial metabolic status is a critical regulatory determinant of PIA synthesis. In addition, these data lead us to propose that the TCA cycle acts as a signal transduction pathway to translate external environmental cues into intracellular metabolic signals that modulate the activity of transcriptional regulators.