A model system for studying the transcriptomic and physiological changes associated with mammalian host-adaptation by Leptospira interrogans serovar Copenhageni.
A model system for studying the transcriptomic and physiological changes associated with mammalian host-adaptation by Leptospira interrogans serovar Copenhageni.
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DOI：
10.1371/journal.ppat.1004004
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发表时间：
2014-03
期刊：
影响因子：
6.7
通讯作者：
Nally JE
中科院分区：
文献类型：
--
作者：
Caimano MJ;Sivasankaran SK;Allard A;Hurley D;Hokamp K;Grassmann AA;Hinton JC;Nally JE
钩端螺旋体病是由钩端螺旋体属螺旋体引起的一种世界性的人畜共患传染病。每年报告的严重钩端螺旋体病病例超过500，000例，其中>10%是致命的。钩端螺旋体在遇到新的宿主之前，可以在适当的潮湿条件下存活数周。水库主机，通常是啮齿动物，表现出很少或没有疾病的迹象，但脱落大量的有机体在他们的尿液。当粘膜表面或擦伤的皮肤接触受感染的尿液或尿液污染的水或土壤时，就会发生传播。在人类中，钩端螺旋体可引起多种临床表现，从无症状或轻度发热到严重黄疸（Weil's）病和肺出血。目前，人们对钩端螺旋体如何在储存宿主中持续存在知之甚少。以前的体外研究表明，钩端螺旋体改变其转录组和蛋白质组学的档案，在哺乳动物感染过程中遇到的环境信号的反应。然而，还没有研究检查哺乳动物宿主适应状态下钩端螺旋体的基因表达。为了更忠实地表达钩端螺旋体如何对宿主来源的信号做出反应，我们使用RNA-Seq比较了钩端螺旋体的转录组。将在透析膜室（DMC）中培养的问号线虫植入大鼠的腹膜腔中，与体外生长的生物体的腹膜腔中的问号线虫进行比较。除了确定“核心”管家基因在两种生长条件下的相对表达水平外，我们还鉴定了166个由L.体内的疑问词我们的分析突出了宿主适应钩端螺旋体有关血红素的吸收和利用的生理方面。我们还确定了11个新的非编码转录本，是候选的小调控RNA。DMC模型提供了一个简单的系统，用于研究与哺乳动物宿主适应相关的转录和抗原变化，选择诱变靶点，以及识别以前未识别的毒力决定簇。钩端螺旋体病是一种由不寻常的钩端螺旋体细菌引起的全球性疾病，由动物传播给人类。钩端螺旋体的致病性物种从受感染动物的尿液中排出，并且在与新的储主或意外宿主接触之前可以在合适的环境中继续存活。钩端螺旋体具有在自然界中传播期间和哺乳动物体内遇到的各种条件下生存的固有能力。然而，我们对促进哺乳动物宿主适应和使钩端螺旋体建立感染的调控途径和基因产物知之甚少。在这项研究中，我们使用了一种新的系统，其中钩端螺旋体培养在透析膜室植入到大鼠的腹膜腔比较哺乳动物宿主适应和体外培养的生物体的基因表达谱。除了提供一个简单的系统，研究哺乳动物感染过程中的转录和生理变化钩端螺旋体进行，我们的数据提供了一个合理的基础，选择新的目标诱变。
Leptospirosis, an emerging zoonotic disease with worldwide distribution, is caused by spirochetes belonging to the genus Leptospira. More than 500,000 cases of severe leptospirosis are reported annually, with >10% of these being fatal. Leptospires can survive for weeks in suitably moist conditions before encountering a new host. Reservoir hosts, typically rodents, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. In humans, leptospires can cause a variety of clinical manifestations, ranging from asymptomatic or mild fever to severe icteric (Weil's) disease and pulmonary haemorrhage. Currently, little is known about how Leptospira persist within a reservoir host. Prior in vitro studies have suggested that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. However, no study has examined gene expression by leptospires within a mammalian host-adapted state. To obtain a more faithful representation of how leptospires respond to host-derived signals, we used RNA-Seq to compare the transcriptome of L. interrogans cultivated within dialysis membrane chambers (DMCs) implanted into the peritoneal cavities of rats with that of organisms grown in vitro. In addition to determining the relative expression levels of “core” housekeeping genes under both growth conditions, we identified 166 genes that are differentially-expressed by L. interrogans in vivo. Our analyses highlight physiological aspects of host adaptation by leptospires relating to heme uptake and utilization. We also identified 11 novel non-coding transcripts that are candidate small regulatory RNAs. The DMC model provides a facile system for studying the transcriptional and antigenic changes associated with mammalian host-adaption, selection of targets for mutagenesis, and the identification of previously unrecognized virulence determinants. Leptospirosis, a global disease caused by the unusual bacterium Leptospira, is transmitted from animals to humans. Pathogenic species of Leptospira are excreted in urine from infected animals and can continue to survive in suitable environments before coming into contact with a new reservoir or accidental host. Leptospires have an inherent ability to survive a wide range of conditions encountered in nature during transmission and within mammals. However, we know very little about the regulatory pathways and gene products that promote mammalian host adaptation and enable leptospires to establish infection. In this study, we used a novel system whereby leptospires are cultivated in dialysis membrane chambers implanted into the peritoneal cavities of rats to compare the gene expression profiles of mammalian host-adapted and in vitro-cultivated organisms. In addition to providing a facile system for studying the transcriptional and physiologic changes leptospires undergo during mammalian infection, our data provide a rational basis for selecting new targets for mutagenesis.
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影响因子：
3.1
作者：
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通讯作者：
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