Cyclic Di-GMP Receptor PlzA Controls Virulence Gene Expression through RpoS in Borrelia burgdorferi
Cyclic Di-GMP Receptor PlzA Controls Virulence Gene Expression through RpoS in Borrelia burgdorferi
复制标题
伯氏疏螺旋体中环状 Di-GMP 受体 PlzA 通过 RpoS 控制毒力基因表达
DOI：
10.1128/iai.01238-13
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发表时间：
2014-01-01
影响因子：
3.1
通讯作者：
Yang, X. Frank
中科院分区：
文献类型：
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作者：
He, Ming;Zhang, Jun-Jie;Yang, X. Frank
摘要莱姆病伯氏疏螺旋体作为一种专性病原体，其基因组只编码两个双组分信号转导系统HK1-Rrp1和Hk2-RRP2(除Chea-Chey系统外)。HK1-Rrp1的输出是第二信使环状双GMP(c-di-GMP)的产物，第二信使是伯氏杆菌在壁虱载体中生存所必需的。Hk2-RRP2的输出是全球调控因子rpos的转录激活，这对于病原体完成其在小鼠之间的传播和建立哺乳动物感染至关重要。尽管有证据表明这两个系统相互通信，但它们是如何连接的还不完全清楚。在本研究中，我们证明了Rrp1的下游效应蛋白c-di-GMP结合蛋白Plza正向调节RRP2的全球调节因子和下游靶标rpos的产生。因此，Plza作为连接HK1-Rrp1和Hk2-RRP2的连接器发挥作用。我们进一步表明，Plza通过在转录和转录后水平上调节另一种调控因子BosR来调节rpos的表达。此外，Plza还能够独立于Rrp1调节rpos的表达，这表明Plza除了是一个c-di-GMP结合蛋白外，还具有其他功能。连同先前发现的Plza控制运动，这些研究表明Plza是一种多功能蛋白质。这些发现进一步强化了伯氏杆菌利用其有限的信号系统和调节器在其复杂的扁虱和哺乳动物之间的地方性循环中管理多个细胞过程的概念。
ABSTRACT As an obligate pathogen, the Lyme disease spirochete Borrelia burgdorferi has a streamlined genome that encodes only two two-component signal transduction systems, Hk1-Rrp1 and Hk2-Rrp2 (in addition to CheA-CheY systems). The output of Hk1-Rrp1 is the production of the second messenger cyclic di-GMP (c-di-GMP), which is indispensable for B. burgdorferi to survive in the tick vector. The output of Hk2-Rrp2 is the transcriptional activation of the global regulator RpoS, which is essential for the pathogen to accomplish its tick-mouse transmission and to establish mammalian infection. Although evidence indicates that these two systems communicate with each other, how they are connected is not fully understood. In this study, we showed that the c-di-GMP-binding protein PlzA, a downstream effector of Rrp1, positively modulates the production of RpoS, a global regulator and downstream target of Rrp2. Thus, PlzA functions as a connector that links Hk1-Rrp1 with Hk2-Rrp2. We further showed that PlzA regulates rpoS expression through modulation of another regulator, BosR, at both the transcriptional and the posttranscriptional levels. In addition, PlzA was also capable of regulating rpoS expression independently of Rrp1, suggesting that besides being a c-di-GMP-binding protein, PlzA has other functions. Along with the previous finding of PlzA controlling motility, these studies demonstrate that PlzA is a multifunctional protein. These findings further reinforce the notion that B. burgdorferi utilizes its limited signaling systems and regulators to govern multiple cellular processes during its complex enzootic cycle between ticks and mammals.