Tracing the origin of Treponema pallidum in China using next-generation sequencing.

Tracing the origin of Treponema pallidum in China using next-generation sequencing.
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利用下一代测序追踪中国梅毒螺旋体的起源

DOI:
10.18632/oncotarget.10154
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发表时间:
2016-07-12
期刊:
影响因子:
--
通讯作者:
Zhou P
Zhou P
中科院分区:
其他
文献类型:
--
作者:
Sun J;Meng Z;Wu K;Liu B;Zhang S;Liu Y;Wang Y;Zheng H;Huang J;Zhou P

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梅毒是由梅毒螺旋体引起的一种全身性传播疾病。螺旋体(TPA)。中国TPA菌株的起源和遗传背景尚不清楚。我们利用新一代测序技术在8株中国TPA菌株中共鉴定出329个单核苷酸变异(snv)。所有TPA菌株聚类为3个谱系,中国TPA菌株聚类为谱系2。系统地理数据表明,TPA菌株的起源早于T. pallidum ssp。香水(TPE)和苍白菌。中国的TPA菌株可能是由世系1和世系3重组而来。此外,我们通过同源性建模分析发现,PBP3蛋白中的非同义取代(I415F)可能会影响PBP3的结构灵活性和底物的结合常数,这可能与T. pallidum的青霉素耐药性有关。我们的研究结果为TPA进化起源的分子基础提供了新的见解,并支持梅毒新诊断/治疗技术的发展。
Syphilis is a systemic sexually transmitted disease caused by Treponema pallidum ssp. pallidum (TPA). The origin and genetic background of Chinese TPA strains remain unclear. We identified a total of 329 single-nucleotide variants (SNVs) in eight Chinese TPA strains using next-generation sequencing. All of the TPA strains were clustered into three lineages, and Chinese TPA strains were grouped in Lineage 2 based on phylogenetic analysis. The phylogeographical data showed that TPA strains originated earlier than did T. pallidum ssp. pertenue (TPE) and T. pallidum ssp. endemicum (TPN) strains and that Chinese TPA strains might be derived from recombination between Lineage 1 and Lineage 3. Moreover, we found through a homology modeling analysis that a nonsynonymous substitution (I415F) in the PBP3 protein might affect the structural flexibility of PBP3 and the binding constant for substrates based on its possible association with penicillin resistance in T. pallidum. Our findings provide new insight into the molecular foundation of the evolutionary origin of TPA and support the development of novel diagnostic/therapeutic technology for syphilis.
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