Study of the Response Regulator Rrp1 Reveals Its Regulatory Role in Chitobiose Utilization and Virulence of Borrelia burgdorferi
Study of the Response Regulator Rrp1 Reveals Its Regulatory Role in Chitobiose Utilization and Virulence of Borrelia burgdorferi
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DOI：
10.1128/iai.00050-13
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发表时间：
2013-05-01
影响因子：
3.1
通讯作者：
Li, Chunhao
中科院分区：
文献类型：
--
作者：
Sze, Ching Wooen;Smith, Alexis;Li, Chunhao
节肢动物和哺乳动物之间的生命周期交替迫使莱姆病螺旋体（伯氏疏螺旋体）通过利用不同的碳水化合物来适应不同的宿主环境。甘油和壳二糖在硬蜱中大量存在。伯氏疏螺旋体可以利用甘油作为糖酵解的碳水化合物来源，并利用壳二糖产生N -乙酰葡糖胺（GlcNAc），它是细菌细胞壁的关键成分。最近的一项研究报告称，Rrp1是一种合成环二鸟苷酸（c - di - GMP）的反应调节因子，它控制着伯氏疏螺旋体中甘油的利用。在本报告中，我们发现当生长培养基中的GlcNAc被壳二糖取代时，rrp1突变体存在生长缺陷，并形成导致细胞裂解的膜泡。基因chbC编码伯氏疏螺旋体的一种关键壳二糖转运蛋白。我们发现chbC的表达水平在突变体中显著受到抑制，并且在突变体中chbC的组成型表达成功挽救了生长缺陷，这表明Rrp1在壳二糖摄取中具有调节作用。免疫印迹和转录研究表明，Rrp1是激活bosR和rpoS所必需的，并且它对chbC的影响很可能是由BosR - RpoS调节途径介导的。蜱 - 小鼠感染研究表明，尽管rrp1突变体无法通过蜱叮咬在小鼠中建立感染，但在未进食的蜱中额外补充GlcNAc可部分挽救感染。此处报道的发现为我们提供了关于Rrp1在伯氏疏螺旋体碳水化合物利用和毒力方面的调节作用的新见解。
Life cycle alternation between arthropod and mammals forces the Lyme disease spirochete, Borrelia burgdorferi, to adapt to different host milieus by utilizing diverse carbohydrates. Glycerol and chitobiose are abundantly present in the Ixodes tick. B. burgdorferi can utilize glycerol as a carbohydrate source for glycolysis and chitobiose to produce N-acetylglucosamine (GlcNAc), a key component of the bacterial cell wall. A recent study reported that Rrp1, a response regulator that synthesizes cyclic diguanylate (c-di-GMP), governs glycerol utilization in B. burgdorferi. In this report, we found that the rrp1 mutant had growth defects and formed membrane blebs that led to cell lysis when GlcNAc was replaced by chitobiose in the growth medium. The gene chbC encodes a key chitobiose transporter of B. burgdorferi. We found that the expression level of chbC was significantly repressed in the mutant and that constitutive expression of chbC in the mutant successfully rescued the growth defect, indicating a regulatory role of Rrp1 in chitobiose uptake. Immunoblotting and transcriptional studies revealed that Rrp1 is required for the activation of bosR and rpoS and that its impact on chbC is most likely mediated by the BosR-RpoS regulatory pathway. Tick-mouse infection studies showed that although the rrp1 mutant failed to establish infection in mice via tick bite, exogenous supplementation of GlcNAc into unfed ticks partially rescued the infection. The finding reported here provides us with new insight into the regulatory role of Rrp1 in carbohydrate utilization and virulence of B. burgdorferi.