Abrogation of ospAB constitutively activates the Rrp2-RpoN-RpoS pathway (sigmaN-sigmaS cascade) in Borrelia burgdorferi.
Abrogation of ospAB constitutively activates the Rrp2-RpoN-RpoS pathway (sigmaN-sigmaS cascade) in Borrelia burgdorferi.
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DOI：
10.1111/j.1365-2958.2008.06491.x
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发表时间：
2008-12
影响因子：
3.6
通讯作者：
Yang XF
中科院分区：
文献类型：
--
作者：
He M;Oman T;Xu H;Blevins J;Norgard MV;Yang XF
伯氏疏螺旋体的两种主要表面脂蛋白和毒力因子OspA和OspC的相互调节的分子机制尚未完全了解。在本文中，我们报告了ospAB操纵子的失活通过Rrp 2-RpoN-RpoS途径的组成性激活导致OspC和许多其他脂蛋白的过量产生。用ospA的野生型拷贝补充ospAB突变体，而不是缺少脂蛋白信号序列的ospA变体，恢复了Rrp 2-RpoN-RpoS途径的正常调节;这些结果表明表型不是由假突变引起的。有趣的是，虽然大多数ospAB突变体克隆显示组成型ospC表达表型，但一些ospAB突变体克隆显示很少或没有ospC表达。进一步的分析表明，这种OspC阴性表型不依赖于ospAB的废除。虽然Rrp 2-RpoN-RpoS通路的激活最近被证明下调ospA，但我们的研究结果表明，OspA的减少也可以激活该通路。我们假设Rrp 2-RpoN-RpoS通路的激活和OspA的下调形成了一个正反馈环，使得螺旋体在蜱虫进食期间产生并维持恒定的高水平的OspC和其他脂蛋白，这是螺旋体传播和哺乳动物感染的关键策略。
Molecular mechanisms underlying the reciprocal regulation of the two major surface lipoproteins and virulence factors of Borrelia burgdorferi, OspA and OspC, are not fully understood. Herein, we report that inactivation of the ospAB operon resulted in overproduction of OspC and many other lipoproteins via the constitutive activation of the Rrp2-RpoN-RpoS pathway. Complementing the ospAB mutant with a wild-type copy of ospA, but not an ospA variant that lacks the lipoprotein signal sequence, restored normal regulation of the Rrp2-RpoN-RpoS pathway; these results indicate that the phenotype was not caused by spurious mutations. Interestingly, while most of the ospAB mutant clones displayed a constitutive ospC expression phenotype, some ospAB mutant clones showed little or no ospC expression. Further analyses revealed that this OspC-negative phenotype was independent of abrogation of ospAB. While activation of the Rrp2-RpoN-RpoS pathway was recently shown to downregulate ospA, our findings suggest that reduction of OspA can also activate this pathway. We postulate that the activation of the Rrp2-RpoN-RpoS pathway and downregulation of OspA form a positive feedback loop that allows spirochaetes to produce and maintain a constant high level of OspC and other lipoproteins during tick feeding, a strategy that is critical for spirochaetal transmission and mammalian infection.
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影响因子：
3.1
作者：
Liang, FT;Yan, J;Fikrig, E
通讯作者：
Fikrig, E
影响因子：
3.2
作者：
Caimano, MJ;Eggers, CH;Radolf, JD
通讯作者：
Radolf, JD
DOI：
10.1073/pnas.0408536102
发表时间：
2005-04-05
影响因子：
11.1
作者：
Fisher, MA;Grimm, D;Gherardini, FC
通讯作者：
Gherardini, FC
小鼠宿主中伯氏毛毛毛毛毛毛虫的分子适应。
影响因子：
15.3
作者：
Liang, Fang Ting;Nelson, F Kenneth;Fikrig, Erol
通讯作者：
Fikrig, Erol
DOI：
10.1084/jem.20011870
发表时间：
2002-02-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Liang FT;Jacobs MB;Bowers LC;Philipp MT
通讯作者：
Philipp MT