Stage-specific global alterations in the transcriptomes of Lyme disease spirochetes during tick feeding and following mammalian host adaptation
Stage-specific global alterations in the transcriptomes of Lyme disease spirochetes during tick feeding and following mammalian host adaptation
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DOI：
10.1111/mmi.12882
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发表时间：
2015-02-01
影响因子：
3.6
通讯作者：
Schwartz, Ira
中科院分区：
文献类型：
--
作者：
Iyer, Radha;Caimano, Melissa J.;Schwartz, Ira
伯氏疏螺旋体是莱姆病的病原体，在自然界中维持在一个涉及哺乳动物宿主和蜱虫媒介的地方性动物循环中。伯氏疏螺旋体的传播、存活和致病潜力取决于该细菌在媒介和宿主之间传播时调节其转录组的能力。在此，我们采用扩增微阵列方法确定了饲养的幼虫、喂养的若虫和在透析膜室中培养的哺乳动物宿主适应生物的伯氏疏螺旋体转录组。结果清楚地表明，螺旋体在每个蜱虫阶段和培养过程中表现出独特的表达谱；重要的是，这些特征中没有一个与体外培养的生物体所表现出的相似。研究人员观察到编码已知或预测的脂蛋白的基因以及参与营养摄取、碳利用和脂质合成的蛋白质的转录水平发生了深刻的变化。趋化相关基因的阶段特异性表达模式也被注意到，这表明趋化机制成分的组成和相互作用在摄食蜱和哺乳动物中有很大差异。这些结果表明，伯氏疏螺旋体的环境感知直接或间接地驱动了细胞包膜成分、趋化性/运动性机制、中间代谢和细胞生理的广泛而紧密结合的调节。这些发现为描述伯氏螺旋体在整个地方性动物循环中的调控途径提供了必要的转录框架，并定义了单个基因对螺旋体在自然界中的生存和对人类的毒力的贡献。
Borrelia burgdorferi, the agent of Lyme disease, is maintained in nature within an enzootic cycle involving a mammalian reservoir and an Ixodes sp. tick vector. The transmission, survival and pathogenic potential of B.burgdorferi depend on the bacterium's ability to modulate its transcriptome as it transits between vector and reservoir host. Herein, we employed an amplification-microarray approach to define the B.burgdorferi transcriptomes in fed larvae, fed nymphs and in mammalian host-adapted organisms cultivated in dialysis membrane chambers. The results show clearly that spirochetes exhibit unique expression profiles during each tick stage and during cultivation within the mammal; importantly, none of these profiles resembles that exhibited by in vitro grown organisms. Profound shifts in transcript levels were observed for genes encoding known or predicted lipoproteins as well as proteins involved in nutrient uptake, carbon utilization and lipid synthesis. Stage-specific expression patterns of chemotaxis-associated genes also were noted, suggesting that the composition and interactivities of the chemotaxis machinery components vary considerably in the feeding tick and mammal. The results as a whole make clear that environmental sensing by B.burgdorferi directly or indirectly drives an extensive and tightly integrated modulation of cell envelope constituents, chemotaxis/motility machinery, intermediary metabolism and cellular physiology. These findings provide the necessary transcriptional framework for delineating B.burgdorferi regulatory pathways throughout the enzootic cycle as well as defining the contribution(s) of individual genes to spirochete survival in nature and virulence in humans.