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柬埔寨恙虫病东方体临床分离株的多样性揭示了其活跃的选择和重组过程。

Diversity of Orientia tsutsugamushi clinical isolates in Cambodia reveals active selection and recombination process.

机构信息

Virology Unit, Institut Pasteur in Cambodia, 5 Monivong blvd, PO Box 983, Phnom Penh, Cambodia.

出版信息

Infect Genet Evol. 2013 Apr;15:25-34. doi: 10.1016/j.meegid.2010.08.015. Epub 2010 Sep 18.

DOI:10.1016/j.meegid.2010.08.015
PMID:20854933
Abstract

Orientia tsutsugamushi, the causative agent of scrub typhus in South East Asia and Pacific, is an obligate intracellular bacterium closely related to the Rickettsia. The pathogen is transmitted to humans through the bites of infected larvae of trombiculid mites of the genus Leptotrombidium in which is maintained trough vertical transmission mechanism. The infection in rodents has been described in over 20 species. Scrub typhus is commonly confused with other tropical fevers and late diagnosis and treatment can lead to severe organ failures and a strain-dependent mortality rate of up to 50%. A MLST scheme associating seven core function genes: adk, lepB, lipA, lipB, secY, sodB and sucA was developed and validated on seven Cambodian strains detected in patients and two complete reference genomes from Korea and Japan. Sequence data were analyzed both with respect to sequence type (ST) diversity and DNA polymorphism. Differing trends were revealed. DNA polymorphism and phylogeny of individual gene loci indicated a significant level of recombination and genetic diversity. However, the ST distribution is clearly clonal and the clinical situation can be summarized by the formula: one patient, one strain, one ST. This contradiction is only apparent and is most likely the consequence of the unique life cycle of O. tsutsugamushi. The quasi exclusive vertical transmission mode in mites generates repeated bottlenecks and small-size populations and strongly limits genetic diversity. O. tsutsugamushi has developed specific mechanisms for generating genetic diversity which include recombination, duplication and conjugation. Recombination and other mechanisms for increasing genetic diversity are likely to occur in rodents which can act as maintenance hosts, although occurrence in mites cannot be excluded. Consequences for the epidemiology of scrub typhus are discussed.

摘要

恙虫病东方体,东南亚和太平洋地区恙虫病的病原体,是一种专性细胞内细菌,与立克次体密切相关。病原体通过感染恙螨属幼虫的叮咬传播给人类,在幼虫中通过垂直传播机制维持。在超过 20 种啮齿动物中已描述了感染。恙虫病常与其他热带热病混淆,延迟诊断和治疗可导致严重器官衰竭和高达 50%的菌株依赖性死亡率。建立并验证了一种 MLST 方案,该方案关联了七个核心功能基因:adk、lepB、lipA、lipB、secY、sodB 和 sucA,用于检测在患者中发现的 7 株柬埔寨菌株和来自韩国和日本的两个完整参考基因组。对序列数据进行了序列类型(ST)多样性和 DNA 多态性分析。揭示了不同的趋势。个别基因座的 DNA 多态性和系统发育表明存在显著水平的重组和遗传多样性。然而,ST 分布明显是克隆的,临床情况可以用公式总结:一个患者,一个菌株,一个 ST。这种矛盾只是表面的,很可能是恙虫病东方体独特的生命周期造成的。螨虫中准专性垂直传播模式产生了反复的瓶颈和小种群,强烈限制了遗传多样性。恙虫病东方体已经开发出了产生遗传多样性的特定机制,包括重组、复制和接合。重组和其他增加遗传多样性的机制可能发生在作为维持宿主的啮齿动物中,尽管不能排除螨虫中的发生。讨论了恙虫病的流行病学后果。

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