The Sensor Kinase KinB Regulates Virulence in Acute Pseudomonas aeruginosa Infection
The Sensor Kinase KinB Regulates Virulence in Acute Pseudomonas aeruginosa Infection
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DOI：
10.1128/jb.01546-10
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发表时间：
2011-06-01
影响因子：
3.2
通讯作者：
Hung, Deborah T.
中科院分区：
文献类型：
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作者：
Chand, Nikhilesh S.;Lee, Jenny See-Wai;Hung, Deborah T.
细菌广泛使用双组件传感器来感知环境并对其做出响应。铜绿假单胞菌拥有细菌中已知的最大的双组分传感器之一，这可能有助于其适应多种环境（包括人类宿主）的独特能力。其中一些双组分传感器，例如 GacS 和 RetS，已被证明在啮齿动物感染模型的毒力中发挥作用。然而，大多数这些双组件传感器的作用和功能仍然未知。斑马鱼是最近鉴定的用于发病机制相关研究的模型宿主，它比哺乳动物模型更适合进行更高通量的分析。使用斑马鱼胚胎作为模型宿主，我们系统地测试了 60 个双组分传感器的作用，并确定了铜绿假单胞菌毒力所需的 6 个传感器。我们发现 KinB 是斑马鱼胚胎急性感染所必需的，并调节许多与毒力相关的表型，包括群体感应、生物膜形成和运动性。它对这些表型的调节独立于其激酶活性和已知的响应调节器 AlgB，这表明它不符合典型的双组分传感器响应调节器模型。
Two-component sensors are widely used by bacteria to sense and respond to the environment. Pseudomonas aeruginosa has one of the largest sets of two-component sensors known in bacteria, which likely contributes to its unique ability to adapt to multiple environments, including the human host. Several of these two-component sensors, such as GacS and RetS, have been shown to play roles in virulence in rodent infection models. However, the role and function of the majority of these two-component sensors remain unknown. Danio rerio is a recently characterized model host for pathogenesis-related studies that is amenable to higher-throughput analysis than mammalian models. Using zebrafish embryos as a model host, we have systematically tested the role of 60 two-component sensors and identified 6 sensors that are required for P. aeruginosa virulence. We found that KinB is required for acute infection in zebrafish embryos and regulates a number of virulence-associated phenotypes, including quorum sensing, biofilm formation, and motility. Its regulation of these phenotypes is independent of its kinase activity and its known response regulator AlgB, suggesting that it does not fit the canonical two-component sensor-response regulator model.