A novel sensor kinase-response regulator hybrid controls biofilm formation and type VI secretion system activity in Burkholderia cenocepacia
A novel sensor kinase-response regulator hybrid controls biofilm formation and type VI secretion system activity in Burkholderia cenocepacia
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DOI：
10.1128/iai.01338-07
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发表时间：
2008-05-01
影响因子：
3.1
通讯作者：
Valvano, Miguel A.
中科院分区：
文献类型：
--
作者：
Aubert, Daniel F.;Flannagan, Ronald S.;Valvano, Miguel A.
盲肠伯克霍尔德氏菌是引起囊性纤维化患者严重慢性感染的一种重要的条件致病菌。棘球绦虫对CF呼吸道的适应可能在感染的持续性中起重要作用。我们已经在B.cenocepacia K56-2中发现了一个名为AtsR的传感器激酶反应调节因子(BCAM0379)，它与铜绿假单胞菌的rets有19%的氨基酸同源性。atsR的失活导致生物膜产量增加，并在非生物表面和肺上皮细胞中都出现了高黏附表型。此外，atsR突变体过度表达和高分泌一种已知由其他革兰氏阴性细菌的VI型分泌系统(T6SS)特异性分泌的Hcp样蛋白。阿米巴空斑分析表明，atsR突变体比野生型菌株更能抵抗网鞭毛虫的捕食，并且这种现象是T6SS依赖的。巨噬细胞感染分析还表明，atsR突变可以诱导巨噬细胞形成肌动蛋白介导的突起，这需要一个功能性的Hcp样蛋白，这表明T6SS参与了肌动蛋白重排。将先前研究中发现的三个在慢性肺部感染模型中对生存造成损害的盲肠弯曲杆菌转座子突变体被定位到T6SS基因簇，表明T6SS是体内感染所必需的。综上所述，我们的数据表明AtsR参与了毒力所需基因的调控，包括编码T6SS的基因。
Burkholderia cenocepacia is an important opportunistic pathogen causing serious chronic infections in patients with cystic fibrosis (CF). Adaptation of B. cenocepacia to the CF airways may play an important role in the persistence of the infection. We have identified a sensor kinase-response regulator (BCAM0379) named AtsR in B. cenocepacia K56-2 that shares 19% amino acid identity with RetS from Pseudomonas aeruginosa.atsR inactivation led to increased biofilm production and a hyperadherent phenotype in both abiotic surfaces and lung epithelial cells. Also, the atsR mutant overexpressed and hypersecreted an Hcp-like protein known to be specifically secreted by the type VI secretion system (T6SS) in other gram-negative bacteria. Amoeba plaque assays demonstrated that the atsR mutant was more resistant to Dictyostelium predation than the wild-type strain and that this phenomenon was T6SS dependent. Macrophage infection assays also demonstrated that the atsR mutant induces the formation of actin-mediated protrusions from macrophages that require a functional Hcp-like protein, suggesting that the T6SS is involved in actin rearrangements. Three B. cenocepacia transposon mutants that were found in a previous study to be impaired for survival in chronic lung infection model were mapped to the T6SS gene cluster, indicating that the T6SS is required for infection in vivo. Together, our data show that AtsR is involved in the regulation of genes required for virulence in B. cenocepacia K56-2, including genes encoding a T6SS.