The diguanylate cyclase, Rrp1, regulates critical steps in the enzootic cycle of the Lyme disease spirochetes.
The diguanylate cyclase, Rrp1, regulates critical steps in the enzootic cycle of the Lyme disease spirochetes.
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DOI：
10.1111/j.1365-2958.2011.07687.x
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发表时间：
2011-07
影响因子：
3.6
通讯作者：
Marconi RT
中科院分区：
文献类型：
--
作者：
Kostick JL;Szkotnicki LT;Rogers EA;Bocci P;Raffaelli N;Marconi RT
Rrp1是伯氏疏螺旋体中唯一产生环二鸟苷酸（二鸟苷酸环化酶）的蛋白质。为了验证Rrp1调节螺旋体在蜱和哺乳动物之间传播所涉及的关键过程这一假设，构建了一个rrp1缺失突变体（B31 - Δrrp1）和一个组成性产生高水平Rrp1的菌株（B31 - OV）。使用硬蜱/C3H - HeJ小鼠模型和蜱浸泡喂养方法评估这些菌株在自然疫源循环中的进展情况。B31 - Δrrp1感染小鼠的效率与野生型相同，但运动能力改变，对N - 乙酰葡糖胺（NAG）的趋化反应降低，在远端器官扩散或定植的能力减弱。虽然该菌株能感染小鼠，但无法在蜱中存活。相反，B31 - OV表现出正常的运动模式和趋化反应，但对小鼠无感染性。通过浸泡喂养技术，我们证明B31 - OV能够在蜱中建立种群，并在接触天然血餐时存活。此处呈现的结果表明，Rrp1以及延伸开来的环二鸟苷酸，对于小鼠感染不是必需的，但对于伯氏疏螺旋体在蜱中成功建立有繁殖能力的种群是必需的。这些分析为遗传调控机制提供了重要的新见解。
Rrp1 is the sole c-di-GMP producing protein (diguanylate cyclase) of Borrelia burgdorferi. To test the hypothesis that Rrp1 regulates critical processes involved in the transmission of spirochetes between ticks and mammals, an rrp1 deletion mutant (B31-Δrrp1) and a strain that constitutively produces elevated levels of Rrp1 (B31-OV) were constructed. The strains were assessed for progression through the enzootic cycle using an Ixodes tick/C3H-HeJ mouse model and tick immersion feeding methods. B31-Δrrp1 infected mice as efficiently as wild type but had altered motility, decreased chemotactic responses to N-acetylglucosamine (NAG) and attenuated ability to disseminate or colonize distal organs. While this strain infected mice, it was not able to survive in ticks. In contrast, the B31-OV displayed normal motility patterns and chemotactic responses but was non-infectious in mice. Using immersion feeding techniques we demonstrate that B31-OV can establish a population in ticks and survive exposure to a natural bloodmeal. The results presented here indicate Rrp1, and by extension, c-di-GMP, are not required for murine infection, but are required for the successful establishment of a productive population of B. burgdorferi in ticks. These analyses provide significant new insight into the genetic regulatory mechanisms
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