The ATP-Dependent Protease ClpP Inhibits Biofilm Formation by Regulating Agr and Cell Wall Hydrolase Sle1 in Staphylococcus aureus
The ATP-Dependent Protease ClpP Inhibits Biofilm Formation by Regulating Agr and Cell Wall Hydrolase Sle1 in Staphylococcus aureus
复制标题
ATP 依赖性蛋白酶 ClpP 通过调节金黄色葡萄球菌中的 Agr 和细胞壁水解酶 Sle1 抑制生物膜形成
DOI：
10.3389/fcimb.2017.00181
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发表时间：
2017-05-15
影响因子：
5.7
通讯作者：
Bae, Taeok
中科院分区：
文献类型：
--
作者：
Liu, Qian;Wang, Xing;Bae, Taeok
生物膜引起留置医疗器械的医院相关感染。在金黄色葡萄球菌中，生物膜的形成是由复杂协调的调节系统网络控制的，其中atp依赖性蛋白酶ClpP表现出抑制作用。在这里，我们证明了ClpP对生物膜形成的抑制作用是通过Agr和细胞壁水解酶Sle1实现的。clpP突变体形成的生物膜由蛋白质和细胞外DNA （eDNA）组成。蛋白质的增加，至少部分是由于突变体的蛋白酶活性降低，这是由agr活性降低引起的。另一方面，eDNA的增加是由于Sle1水平升高导致细胞裂解增加。事实上，与野生型相比，clpP突变体分泌的eDNA水平增加，对triton诱导的自溶表现出更高的敏感性。clpP突变体中sle1的缺失使生物膜的形成、eDNA的水平和triton诱导的自溶降低到野生型水平。然而，尽管增强了生物膜形成能力，clpP突变体在小鼠皮下异物感染模型中显示出显著降低的毒力，这表明增强的生物膜形成能力不能弥补clpP在感染过程中的内在功能。
Biofilm causes hospital-associated infections on indwelling medical devices. In Staphylococcus aureus, Biofilm formation is controlled by intricately coordinated network of regulating systems, of which the ATP-dependent protease ClpP shows an inhibitory effect. Here, we demonstrate that the inhibitory effect of ClpP on biofilm formation is through Agr and the cell wall hydrolase Sle1. Biofilm formed by clpP mutant consists of proteins and extracellular DNA (eDNA). The increase of the protein was, at least in part, due to the reduced protease activity of the mutant, which was caused by the decreased activity of agr. On the other hand, the increase of eDNA was due to increased cell lysis caused by the higher level of Sle1. Indeed, as compared with wild type, the clpP mutant excreted an increased level of eDNA, and showed higher sensitivity to Triton-induced autolysis. The deletion of sle1 in the clpP mutant decreased the biofilm formation, the level of eDNA, and the Triton-induced autolysis to wild-type levels. Despite the increased biofilm formation capability, however, the clpP mutant showed significantly reduced virulence in a murine model of subcutaneous foreign body infection, indicating that the increased biofilm formation capability cannot compensate for the intrinsic functions of ClpP during infection.