Proteomic Analysis of Leptospira interrogans Shed in Urine of Chronically Infected Hosts
Proteomic Analysis of Leptospira interrogans Shed in Urine of Chronically Infected Hosts
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DOI：
10.1128/iai.00511-08
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发表时间：
2008-11-01
影响因子：
3.1
通讯作者：
Nally, Jarlath E.
中科院分区：
文献类型：
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作者：
Monahan, Avril M.;Callanan, John J.;Nally, Jarlath E.
钩端螺旋体病是一种全球性的人畜共患病。病原体，致病性钩端螺旋体，存活于慢性感染宿主的肾小管中，钩端螺旋体从那里通过尿液脱落到环境中。新宿主的感染可以表现为一系列急性和慢性疾病过程，反映宿主-病原体相互作用的变化。本研究旨在重现褐家鼠感染钩端螺旋体的带菌者阶段，从而促进尿液中钩端螺旋体的脱落。收集尿液中脱落的钩端螺旋体进行蛋白质组学分析，因为这些生物体反映了与新宿主感染相关的钩端螺旋体的天然毒性形式。实验性感染的大鼠在临床上无症状，但在几个月的尿液中排出浓度高达107个钩端螺旋体/ml尿液的钩端螺旋体。蛋白质组学分析的大鼠尿液分离的钩端螺旋体相比，在体外培养的钩端螺旋体证实差异蛋白和抗原表达，如通过二维凝胶电泳和免疫印迹。此外，虽然从慢性感染的大鼠的血清与许多抗原的体外培养的钩端螺旋体，一些抗原的大鼠尿液分离的钩端螺旋体反应。结果证实，在慢性感染过程中钩端螺旋体的差异蛋白质表达促进其持久性存在的特异性宿主抗体反应。
Leptospirosis is a global zoonotic disease. The causative agent, pathogenic Leptospira species, survives in the renal tubules of chronically infected hosts, from where leptospires are shed via urine into the environment. Infection of new hosts can present as an array of acute and chronic disease processes reflecting variations in host-pathogen interactions. The present study was designed to reproduce the carrier phase of infection in Rattus norvegicus, thus facilitating shedding of leptospires in urine. Leptospires shed in urine were collected for proteomic analysis because these organisms reflect a naturally virulent form of Leptospira associated with infection of new hosts. Experimentally infected rats remained clinically asymptomatic but shed leptospires in urine for several months at concentrations of up to 107 leptospires/ml of urine. Proteomic analysis of rat urine-isolated leptospires compared to in vitro-cultivated leptospires confirmed differential protein and antigen expression, as demonstrated by two-dimensional gel electrophoresis and immunoblotting. Furthermore, while serum from chronically infected rats reacted with many antigens of in vitro-cultivated Leptospira, few antigens of rat urine-isolated Leptospira were reactive. Results confirm that differential protein expression by Leptospira during chronic infection facilitates its persistence in the presence of a specific host antibody response.