Using NMR Metabolomics to Investigate Tricarboxylic Acid Cycle-dependent Signal Transduction in Staphylococcus epidermidis
Using NMR Metabolomics to Investigate Tricarboxylic Acid Cycle-dependent Signal Transduction in Staphylococcus epidermidis
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DOI：
10.1074/jbc.m110.152843
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发表时间：
2010-11-19
影响因子：
4.8
通讯作者：
Somerville, Greg A.
中科院分区：
文献类型：
--
作者：
Sadykov, Marat R.;Zhang, Bo;Somerville, Greg A.
表皮葡萄球菌是一种皮肤常驻细菌，也是生物材料相关感染的主要原因。从驻留在皮肤上到驻留在植入的生物材料上的转变伴随着促进细菌在新环境中存活的调节变化。这些调节变化取决于细菌“感知”环境变化的能力。In S.在表皮，不同的环境信号可以影响生物膜基质多糖细胞间粘附素（PIA）的合成。以前，我们证明了PIA的生物合成是由三羧酸（TCA）循环活性调节。观察到非常不同的环境信号导致共同的表型（即PIA合成增加）并且TCA循环活性调节PIA生物合成，这使我们假设S.表皮细胞通过调节TCA循环活性来“感知”不同的环境信号。在这项研究中，我们使用NMR代谢组学来证明，不同的环境信号被转换成常见的代谢组学变化，这些变化被代谢物响应调节因子（如CcpA）“感知”，从而影响PIA的生物合成。这些数据阐明了一种机制，即非常不同的环境信号引起共同的表型变化。此外，由于TCA循环在不同细菌属中的频率和TCA循环酶的内在性质，TCA循环可能在许多细菌中充当信号转导途径。
Staphylococcus epidermidis is a skin-resident bacterium and a major cause of biomaterial-associated infections. The transition from residing on the skin to residing on an implanted biomaterial is accompanied by regulatory changes that facilitate bacterial survival in the new environment. These regulatory changes are dependent upon the ability of bacteria to "sense" environmental changes. In S. epidermidis, disparate environmental signals can affect synthesis of the biofilm matrix polysaccharide intercellular adhesin (PIA). Previously, we demonstrated that PIA biosynthesis is regulated by tricarboxylic acid (TCA) cycle activity. The observations that very different environmental signals result in a common phenotype (i.e. increased PIA synthesis) and that TCA cycle activity regulates PIA biosynthesis led us to hypothesize that S. epidermidis is "sensing" disparate environmental signals through the modulation of TCA cycle activity. In this study, we used NMR metabolomics to demonstrate that divergent environmental signals are transduced into common metabolomic changes that are "sensed" by metabolite-responsive regulators, such as CcpA, to affect PIA biosynthesis. These data clarify one mechanism by which very different environmental signals cause common phenotypic changes. In addition, due to the frequency of the TCA cycle in diverse genera of bacteria and the intrinsic properties of TCA cycle enzymes, it is likely the TCA cycle acts as a signal transduction pathway in many bacteria.