The Pseudomonas aeruginosa PilSR Two-Component System Regulates Both Twitching and Swimming Motilities.
The Pseudomonas aeruginosa PilSR Two-Component System Regulates Both Twitching and Swimming Motilities.
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DOI：
10.1128/mbio.01310-18
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发表时间：
2018-07-24
期刊：
影响因子：
6.4
通讯作者：
Burrows LL
中科院分区：
文献类型：
--
作者：
Kilmury SLN;Burrows LL
对于许多细菌病原体来说，运动性是一个重要的毒力特征，使它们能够在适当的时间将自己定位在适当的位置。IV型菌毛和鞭毛的运动结构也参与感知表面接触，从而调节致病性。在铜绿假单胞菌中，PILS-PilR双组分系统(TCS)调控IV型菌毛(T4P)主要亚基PilA的表达，而单极鞭毛的生物合成受包括FleSR TCS的分级系统的调节。先前对硫磺还原地杆菌和结节双歧杆菌的研究表明，PilR参与调控非T4P相关基因，包括一些参与鞭毛生物合成的基因。在这里，我们使用转录组测序(RNA-seq)分析来鉴定除了PILA之外的基因，以及在没有PILR的情况下表达发生变化的基因。在已鉴定的基因中，有10个基因在Pila突变体中转录增加，而在PilR突变体中转录减少，尽管这两个突变体都缺乏T4P和菌毛相关的表型。这些反向失调基因的产物，其中许多是假设的，可能对毒力和表面相关行为重要，因为突变体改变了线虫模型中的群体运动、生物膜形成、VI型分泌系统表达和致病性。此外，PilSR TCS正向调控FleSR的转录，从而调节FleSR调节子中的许多基因。结果表明，PilSR缺失突变体在游泳运动方面存在缺陷，这种缺陷与PilA的缺失无关。综上所述，这些数据表明，除了控制T4P的表达外，PilSR还可能在调节铜绿假单胞菌的运动和表面感知行为方面发挥更广泛的作用。表面附属物，如IV型菌毛和鞭毛，对于在宿主体内建立表面附着和感染是重要的，以响应适当的提示。在铜绿假单胞菌中，控制IV型菌毛表达的PilSR调控系统在主要Pilin PilA的表达中具有既定的作用。在这里，我们提供了证据，支持PilSR在调节鞭毛依赖的游泳运动和毛发依赖的抽动运动方面发挥新的作用。此外，尽管PilA和PilR突变体都缺乏PilA和PilI，但我们发现了在PilA突变体中下调而在PilA突变体中上调的基因集，以及仅在PilR突变体中下调的基因，而不依赖于Pilus的表达。这一发现表明，PilA内膜水平的变化只是PilR调节基因表达的信号之一。将PilR确定为多条运动通路的调节因子，可能使其成为抗毒力化合物的有趣的治疗靶点。
Motility is an important virulence trait for many bacterial pathogens, allowing them to position themselves in appropriate locations at appropriate times. The motility structures type IV pili and flagella are also involved in sensing surface contact, which modulates pathogenicity. In Pseudomonas aeruginosa, the PilS-PilR two-component system (TCS) regulates expression of the type IV pilus (T4P) major subunit PilA, while biosynthesis of the single polar flagellum is regulated by a hierarchical system that includes the FleSR TCS. Previous studies of Geobacter sulfurreducens and Dichelobacter nodosus implicated PilR in regulation of non-T4P-related genes, including some involved in flagellar biosynthesis. Here we used transcriptome sequencing (RNA-seq) analysis to identify genes in addition to pilA with changes in expression in the absence of pilR. Among the genes identified were 10 genes whose transcription increased in the pilA mutant but decreased in the pilR mutant, despite both mutants lacking T4P and pilus-related phenotypes. The products of these inversely dysregulated genes, many of which were hypothetical, may be important for virulence and surface-associated behaviors, as mutants had altered swarming motility, biofilm formation, type VI secretion system expression, and pathogenicity in a nematode model. Further, the PilSR TCS positively regulated transcription of fleSR, and thus many genes in the FleSR regulon. As a result, pilSR deletion mutants had defects in swimming motility that were independent of the loss of PilA. Together, these data suggest that in addition to controlling T4P expression, PilSR could have a broader role in the regulation of P. aeruginosa motility and surface sensing behaviors. Surface appendages such as type IV pili and flagella are important for establishing surface attachment and infection in a host in response to appropriate cues. The PilSR regulatory system that controls type IV pilus expression in Pseudomonas aeruginosa has an established role in expression of the major pilin PilA. Here we provide evidence supporting a new role for PilSR in regulating flagellum-dependent swimming motility in addition to pilus-dependent twitching motility. Further, even though both pilA and pilR mutants lack PilA and pili, we identified sets of genes downregulated in the pilR mutant and upregulated in a pilA mutant as well as genes downregulated only in a pilR mutant, independent of pilus expression. This finding suggests that change in the inner membrane levels of PilA is only one of the cues to which PilR responds to modulate gene expression. Identification of PilR as a regulator of multiple motility pathways may make it an interesting therapeutic target for antivirulence compounds.