Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster

Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster
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DOI:
10.1038/nmicrobiol.2016.245
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发表时间:
2017-01-01
影响因子:
28.3
通讯作者:
Bagheri, Homayoun C.
Bagheri, Homayoun C.
中科院分区:
生物学1区
文献类型:
--
作者:
Arora, Natasha;Schuenemann, Verena J.;Bagheri, Homayoun C.

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世纪后期开始的梅毒大流行的突然袭击确立了这种毁灭性的传染病是人类历史上最可怕的疾病之一。令人惊讶的是,尽管自世纪中期以来有效的抗生素治疗是可用的,但这种由梅毒螺旋体梅毒亚种引起的细菌感染仍然存在。梅毒(TPA)在过去几十年中重新出现在全球,2008年估计有1060万例(参考文献2)。虽然尚未发现对青霉素的耐药性,但越来越多的菌株对二线抗生素阿奇霉素无效(3)。由于临床样本中密螺旋体DNA的含量低以及培养病原体的困难,对当前感染的遗传模式或疾病的进化起源知之甚少(4)。在这里,我们使用DNA捕获和全基因组测序成功地询问了梅毒患者标本的全基因组变异,结合TPA和其他两个亚种的实验室样本。基于测序的基因组的系统发育比较表明,TPA菌株检查后,十五世纪,在近代早期的共同祖先。此外,大多数当代菌株是阿奇霉素耐药的,并且是一个全球主导簇的成员,在此命名为SS 14-Omega。世纪中期,抗生素的发现使该集群从一个共同的祖先开始多样化。它最近的系统发育分化和全球存在指向一个大流行菌株集群的出现。
The abrupt onslaught of the syphilis pandemic that started in the late fifteenth century established this devastating infectious disease as one of the most feared in human history(1). Surprisingly, despite the availability of effective antibiotic treatment since the mid-twentieth century, this bacterial infection, which is caused by Treponema pallidum subsp. pallidum (TPA), has been re-emerging globally in the last few decades with an estimated 10.6 million cases in 2008 (ref. 2). Although resistance to penicillin has not yet been identified, an increasing number of strains fail to respond to the second-line antibiotic azithromycin(3). Little is known about the genetic patterns in current infections or the evolutionary origins of the disease due to the low quantities of treponemal DNA in clinical samples and difficulties in cultivating the pathogen(4). Here, we used DNA capture and whole-genome sequencing to successfully interrogate genome-wide variation from syphilis patient specimens, combined with laboratory samples of TPA and two other subspecies. Phylogenetic comparisons based on the sequenced genomes indicate that the TPA strains examined share a common ancestor after the fifteenth century, within the early modern era. Moreover, most contemporary strains are azithromycin-resistant and are members of a globally dominant cluster, named here as SS14-Omega. The cluster diversified from a common ancestor in the mid-twentieth century subsequent to the discovery of antibiotics. Its recent phylogenetic divergence and global presence point to the emergence of a pandemic strain cluster.