Molecular insights into the master regulator CysB-mediated bacterial virulence in Pseudomonas aeruginosa
Molecular insights into the master regulator CysB-mediated bacterial virulence in Pseudomonas aeruginosa
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铜绿假单胞菌主调节因子 CysB 介导的细菌毒力的分子研究
DOI：
10.1111/mmi.14200
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发表时间：
2019
影响因子：
3.6
通讯作者：
Liang Haihua
中科院分区：
文献类型：
--
作者：
Song Yaqin;Yang Chun;Chen Gukui;Zhang Yixi;Seng Zijing;Cai Zhao;Zhang Chao;Yang Liang;Gan Jianhua;Liang Haihua
铜绿假单胞菌是引起人类严重急性和慢性感染的主要病原体。III型分泌系统(T3SS)是一种重要的毒力因子，在急性感染中起重要作用。然而，T3SS的调控机制尚不完全清楚。在本研究中，我们发现，CysB的缺失降低了T3SS基因的表达和聚集运动，但促进了生物膜的形成。在小鼠急性肺炎模型中，与野生型相比，cysB突变降低了平均细菌负荷。进一步的实验证明，CysB通过直接调节传感器激酶rets参与T3SS基因表达的降低和细菌的致病。我们还进行了PaCysB的结晶学研究。PaCysB NTD结构域的整体折叠与其他LysR超家族蛋白相似，结构叠加揭示了PaCysB可能的DNA结合模式。结构比较也揭示了PaCysB Rd结构域的极大灵活性，它可能在靶DNA的弯曲和转录调控中发挥重要作用。综上所述，这些结果扩大了我们目前对T3SS和RETS通路复杂调控网络的理解。CysB的晶体结构为研究其同系物在其他细菌物种中的功能提供了新的见解。
Pseudomonas aeruginosais a major pathogen that causes serious acute and chronic infections in humans. The type III secretion system (T3SS) is an important virulence factor that plays essential roles in acute infections. However, the regulatory mechanisms of T3SS are not fully understood. In this study, we found that the deletion ofcysBreduced the T3SS gene expression and swarming motility but enhanced biofilm formation. In a mouse acute pneumonia model, mutation ofcysBdecreased the average bacterial load compared to that of the wild‐type strain. Further experiments demonstrated that CysB contributed to the reduced T3SS gene expression and bacterial pathogenesis by directly regulating the sensor kinase RetS. We also performed crystallographic studies of PaCysB. The overall fold of PaCysB NTD domain is similar to other LysR superfamily proteins and structural superposition revealed one possible DNA‐binding model for PaCysB. Structural comparison also revealed great flexibility of the PaCysB RD domain, which may play an important role in bending and transcriptional regulation of target DNA. Taken together, these results expand our current understanding of the complex regulatory networks of T3SS and RetS pathways. The crystal structure of CysB provides new insights for studying the function of its homologs in other bacterial species.