Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira.
Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira.
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DOI：
10.3389/fcimb.2018.00045
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发表时间：
2018
影响因子：
5.7
通讯作者：
Ko AI
中科院分区：
文献类型：
--
作者：
Adhikarla H;Wunder EA Jr;Mechaly AE;Mehta S;Wang Z;Santos L;Bisht V;Diggle P;Murray G;Adler B;Lopez F;Townsend JP;Groisman E;Picardeau M;Buschiazzo A;Ko AI
钩端螺旋体病是一种新出现的人畜共患疾病，每年有100多万例病例。目前缺乏证据表明信号通路参与了钩端螺旋体的感染过程。在我们对20种钩端螺旋体的综合基因组分析中，我们鉴定了七种病原体特异性双组分系统（TCS）蛋白。破坏致病性钩端螺旋体菌株中的两个TCS基因导致钩端螺旋体病仓鼠模型中的毒力丧失。相应的基因lvrA和lvrB（钩端螺旋体毒力调节因子）并列在一个操纵子，并预测编码一个混合组氨酸激酶和混合反应调节因子，分别。对破坏一个（lvr B）或两个基因（lvr A/B）的lvr突变株的转录组分析揭示了850个差异表达基因的全局转录调控。磷酸转移试验表明，LvrA磷酸化LvrB和预测进一步的信号下游的一个或多个DNA结合反应调节剂，这表明它是一个分支的途径。系统发育分析表明，lvrA和lvrB通过基因复制在钩端螺旋体的不同生态谱系中独立进化。这项研究揭示了一种调节致病性钩端螺旋体（Lvr）毒力的新信号通路，为了解这种危及生命的细菌中调节的分子基础提供了一个框架。
Leptospirosis is an emerging zoonotic disease with more than 1 million cases annually. Currently there is lack of evidence for signaling pathways involved during the infection process of Leptospira. In our comprehensive genomic analysis of 20 Leptospira spp. we identified seven pathogen-specific Two-Component System (TCS) proteins. Disruption of two these TCS genes in pathogenic Leptospira strain resulted in loss-of-virulence in a hamster model of leptospirosis. Corresponding genes lvrA and lvrB (leptospira virulence regulator) are juxtaposed in an operon and are predicted to encode a hybrid histidine kinase and a hybrid response regulator, respectively. Transcriptome analysis of lvr mutant strains with disruption of one (lvrB) or both genes (lvrA/B) revealed global transcriptional regulation of 850 differentially expressed genes. Phosphotransfer assays demonstrated that LvrA phosphorylates LvrB and predicted further signaling downstream to one or more DNA-binding response regulators, suggesting that it is a branched pathway. Phylogenetic analyses indicated that lvrA and lvrB evolved independently within different ecological lineages in Leptospira via gene duplication. This study uncovers a novel-signaling pathway that regulates virulence in pathogenic Leptospira (Lvr), providing a framework to understand the molecular bases of regulation in this life-threatening bacterium.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
6.7
作者：
Caimano MJ;Sivasankaran SK;Allard A;Hurley D;Hokamp K;Grassmann AA;Hinton JC;Nally JE
通讯作者：
Nally JE
DOI：
10.1073/pnas.1404097111
发表时间：
2014-06-10
影响因子：
11.1
作者：
Espinosa, Javier;Rodriguez-Mateos, Francisco;Contreras, Asuncion
通讯作者：
Contreras, Asuncion
影响因子：
3.2
作者：
JOHNSON, RC;HARRIS, VG
通讯作者：
HARRIS, VG
DOI：
10.1073/pnas.202353699
发表时间：
2002-10-15
影响因子：
11.1
作者：
Graham, MR;Smoot, LM;Musser, JM
通讯作者：
Musser, JM