Regulation of the Sae Two-Component System by Branched-Chain Fatty Acids in Staphylococcus aureus.
Regulation of the Sae Two-Component System by Branched-Chain Fatty Acids in Staphylococcus aureus.
复制标题
DOI：
10.1128/mbio.01472-22
复制
发表时间：
2022-10-26
期刊：
影响因子：
6.4
通讯作者：
Brinsmade, Shaun R.
中科院分区：
文献类型：
--
作者：
Pendleton, Augustus;Yeo, Won-Sik;Alqahtani, Shahad;DiMaggio, Dennis A., Jr.;Stone, Carl J.;Li, Zhaotao;Singh, Vineet K.;Montgomery, Christopher P.;Bae, Taeok;Brinsmade, Shaun R.
关键词：
金黄色葡萄球菌是一种普遍存在的革兰氏阳性细菌和机会性人类病原体。金黄色葡萄球菌的发病机制依赖于一个复杂的调节基因表达的调控因子网络。这个网络中的两个重要因子是CodY，一种对营养可用性有反应的抑制蛋白，以及SaeRS双组分系统（TCS），它对中性粒细胞产生的因子有反应。我们之前的工作表明，CodY通过一种未知的机制间接地通过Sae调节许多毒素的分泌。我们报道，codY的破坏导致磷酸化的SaeR （SaeR~P）水平增加，并且codY突变的细胞膜比野生型细胞膜含有更高百分比的支链脂肪酸（BCFAs），这促使我们假设膜组成的变化调节了SaeS传感器激酶的活性。破坏编码二氢脂酰脱氢酶（对BCFA合成至关重要）的lpdA基因，可显著降低膜中SaeR、磷酸化SaeR和BCFA的丰度，从而减少毒素产生和减弱毒力。较低的SaeR水平可以部分解释为稳定性降低。lpdA突变体中的Sae活性可以与外源短长度或全长BCFAs在遗传和化学上互补。有趣的是，缺乏lpdA也会改变其他tcs的活性，这表明特定的BCFA要求管理多个tcs的基础活性。这些结果揭示了一种通过BCFA合成转录后毒力调节的新方法，可能将CodY活性与金黄色葡萄球菌的多种毒力调节因子联系起来。
Staphylococcus aureus is a ubiquitous Gram-positive bacterium and an opportunistic human pathogen. S. aureus pathogenesis relies on a complex network of regulatory factors that adjust gene expression. Two important factors in this network are CodY, a repressor protein responsive to nutrient availability, and the SaeRS two-component system (TCS), which responds to neutrophil-produced factors. Our previous work revealed that CodY regulates the secretion of many toxins indirectly via Sae through an unknown mechanism. We report that disruption of codY results in increased levels of phosphorylated SaeR (SaeR~P) and that codY mutant cell membranes contain a higher percentage of branched-chain fatty acids (BCFAs) than do wild-type membranes, prompting us to hypothesize that changes to membrane composition modulate the activity of the SaeS sensor kinase. Disrupting the lpdA gene encoding dihydrolipoyl dehydrogenase, which is critical for BCFA synthesis, significantly reduced the abundance of SaeR, phosphorylated SaeR, and BCFAs in the membrane, resulting in reduced toxin production and attenuated virulence. Lower SaeR levels could be explained in part by reduced stability. Sae activity in the lpdA mutant could be complemented genetically and chemically with exogenous short- or full-length BCFAs. Intriguingly, lack of lpdA also alters the activity of other TCSs, suggesting a specific BCFA requirement managing the basal activity of multiple TCSs. These results reveal a novel method of posttranscriptional virulence regulation via BCFA synthesis, potentially linking CodY activity to multiple virulence regulators in S. aureus.
登录
查看更多内容
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
影响因子：
3.6
作者：
DeMars ZR;Krute CN;Ridder MJ;Gilchrist AK;Menjivar C;Bose JL
通讯作者：
Bose JL
影响因子：
3.6
作者：
Jeong DW;Cho H;Jones MB;Shatzkes K;Sun F;Ji Q;Liu Q;Peterson SN;He C;Bae T
通讯作者：
Bae T
影响因子：
6.7
作者：
Cho H;Jeong DW;Liu Q;Yeo WS;Vogl T;Skaar EP;Chazin WJ;Bae T
通讯作者：
Bae T
影响因子：
3.2
作者：
Dubrac, S;Msadek, T
通讯作者：
Msadek, T