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A Bacillus anthracis Genome Sequence from the Sverdlovsk 1979 Autopsy Specimens

机译:斯维尔德洛夫斯克1979年尸检标本的炭疽杆菌基因组序列

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ABSTRACT Anthrax is a zoonotic disease that occurs naturally in wild and domestic animals but has been used by both state-sponsored programs and terrorists as a biological weapon. A Soviet industrial production facility in Sverdlovsk, USSR, proved deficient in 1979 when a plume of spores was accidentally released and resulted in one of the largest known human anthrax outbreaks. In order to understand this outbreak and others, we generated a Bacillus anthracis population genetic database based upon whole-genome analysis to identify all single-nucleotide polymorphisms (SNPs) across a reference genome. Phylogenetic analysis has defined three major clades (A, B, and C), B and C being relatively rare compared to A. The A clade has numerous subclades, including a major polytomy named the trans-Eurasian (TEA) group. The TEA radiation is a dominant evolutionary feature of B.?anthracis , with many contemporary populations having resulted from a large spatial dispersal of spores from a single source. Two autopsy specimens from the Sverdlovsk outbreak were deep sequenced to produce draft B.?anthracis genomes. This allowed the phylogenetic placement of the Sverdlovsk strain into a clade with two Asian live vaccine strains, including the Russian Tsiankovskii strain. The genome was examined for evidence of drug resistance manipulation or other genetic engineering, but none was found. The Soviet Sverdlovsk strain genome is consistent with a wild-type strain from Russia that had no evidence of genetic manipulation during its industrial production. This work provides insights into the world’s largest biological weapons program and provides an extensive B.?anthracis phylogenetic reference. IMPORTANCE The 1979 Russian anthrax outbreak resulted from an industrial accident at the Soviet anthrax spore production facility in the city of Sverdlovsk. Deep genomic sequencing of two autopsy specimens generated a draft genome and phylogenetic placement of the Soviet Sverdlovsk anthrax strain. While it is known that Soviet scientists had genetically manipulated Bacillus anthracis with the potential to evade vaccine prophylaxis and antibiotic therapeutics, there was no genomic evidence of this from the Sverdlovsk production strain genome. The whole-genome SNP genotype of the Sverdlovsk strain was used to precisely identify it and its close relatives in the context of an extensive global B.?anthracis strain collection. This genomic identity can now be used for forensic tracking of this weapons material on a global scale and for future anthrax investigations.
机译:摘要炭疽病是一种人畜共患病,在野生动物和家养动物中自然发生,但由国家资助的计划和恐怖分子已将其用作生物武器。 1979年,苏联在斯维尔德洛夫斯克的一家工业生产设施被证明是有缺陷的,当时意外释放出一股孢子,这是已知的最大的人类炭疽暴发之一。为了了解这次疫情和其他疫情,我们基于全基因组分析生成了炭疽芽孢杆菌种群遗传数据库,以鉴定参考基因组中的所有单核苷酸多态性(SNP)。系统发育分析已定义了三个主要进化枝(A,B和C),与A相比,B和C相对较少。A进化枝具有许多子进化枝,包括称为跨欧亚(TEA)组的主要多角体切开术。 TEA辐射是炭疽杆菌的主要进化特征,许多当代种群是由于单一来源的大量孢子在空间上扩散而产生的。对来自斯维尔德洛夫斯克疫情的两个尸检标本进行深度测序,以产​​生拟南芥炭疽病基因组。这使得系统发育上的斯维尔德洛夫斯克病毒株与两个亚洲活疫苗株(包括俄罗斯的先科夫斯基病毒株)一起进化为进化枝。检查了基因组是否有耐药性操纵或其他基因工程的证据,但没有发现。苏联的斯维尔德洛夫斯克(Sverdlovsk)菌株基因组与来自俄罗斯的野生型菌株一致,该菌株在其工业生产过程中没有基因操纵的迹象。这项工作为世界上最大的生物武器计划提供了见识,并为炭疽杆菌的系统发育提供了广泛的参考。重要信息1979年俄罗斯炭疽病暴发是由于斯维尔德洛夫斯克市苏联炭疽病孢子生产设施发生的工业事故造成的。对两个尸检标本进行深度基因组测序,得出了苏联Sverdlovsk炭疽病毒株的基因组草图和系统发育位置。众所周知,苏联科学家对炭疽芽孢杆菌进行了基因操纵,可能逃避疫苗的预防和抗生素治疗,但从斯维尔德洛夫斯克生产菌株的基因组来看,尚无基因组学证据。 Sverdlovsk菌株的全基因组SNP基因型在广泛的全球炭疽芽孢杆菌菌株收集中被用来精确识别其及其近亲。这种基因组身份现在可用于在全球范围内对该武器材料进行法医追踪,并用于将来的炭疽调查。

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