Whole genome sequencing of Borrelia burgdorferi isolates reveals linked clusters of plasmid-borne accessory genome elements associated with virulence.
Whole genome sequencing of Borrelia burgdorferi isolates reveals linked clusters of plasmid-borne accessory genome elements associated with virulence.
复制标题
伯氏疏螺旋体分离株的全基因组测序揭示了与毒力相关的质粒携带的辅助基因组元件的连锁簇。
DOI：
10.1101/2023.02.26.530159
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Li
中科院分区：
文献类型：
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作者：
Lemieux,JacobE;Huang,Weihua;Hill,Nathan;Cerar,Tjasa;Freimark,Lisa;Hernandez,Sergio;Luban,Matteo;Maraspin,Vera;Bogovic,Petra;Ogrinc,Katarina;Ruzic-Sabljic,Eva;Lapierre,Pascal;Lasek-Nesselquist,Erica;Singh,Navjot;Iyer,Radha;Li
莱姆病是北美和欧洲最常见的媒介传播疾病。莱姆病的临床表现因感染伯氏疏螺旋体的基因种类而异，但这些关联背后的微生物遗传因素尚不清楚。在这里，我们报告了来自美国东部、中西部和中欧患者的299株患者来源的伯氏杆菌感觉受限伯氏杆菌(BBS)的全基因组序列(WGS)和分析。我们开发了基于WGS的BBS分离株的分类，证实和扩展了先前的单基因和多基因座分型系统的发现，定义了人感染的BBS分离株的质粒谱，注释了核心和菌株可变的表面脂蛋白组学，并确定了与播散性感染相关的基因座。几乎所有的分离株都有一个由800个开放阅读框组成的核心基因组和一套由lp17、lp25、lp36、lp28-3、lp28-4、lp54和cp26组成的核心质粒组。变株(辅助)质粒和基因与系统发育密切相关。使用遗传关联研究方法，我们确定了与传播相关的辅助基因组签名，并定义了组成该签名的单个质粒和基因。RST1/WGS A亚组中的菌株，特别是以OspC A型基因型为标志的亚组，与更高的传播率相关。OspC A型毒株具有独特的强连锁遗传改变，包括lp56和lp28-1质粒的存在，以及一组基因，这些基因可能有助于与其他基因型相比提高其毒力。OspC A型毒株的模式代表了BBS分离株中更广泛的范例，其中遗传结构由主要位于质粒上的相关的菌株可变基因组定义，特别是对于表面暴露的脂蛋白的表达。这些基因簇通过特定菌株的质粒群模式进行遗传，并与侵袭性感染的可能性有关。
Lyme disease is the most common vector-borne disease in North America and Europe. The clinical manifestations of Lyme disease vary based on the genospecies of the infecting Borrelia burgdorferi spirochete, but the microbial genetic elements underlying these associations are not known. Here, we report the whole genome sequence (WGS) and analysis of 299 patient-derived B. burgdorferi sensu stricto (Bbss) isolates from patients in the Eastern and Midwestern US and Central Europe. We develop a WGS-based classification of Bbss isolates, confirm and extend the findings of previous single- and multi-locus typing systems, define the plasmid profiles of human-infectious Bbss isolates, annotate the core and strain-variable surface lipoproteome, and identify loci associated with disseminated infection. A core genome consisting of ~800 open reading frames and a core set of plasmids consisting of lp17, lp25, lp36, lp28-3, lp28-4, lp54, and cp26 are found in nearly all isolates. Strain-variable (accessory) plasmids and genes correlate strongly with phylogeny. Using genetic association study methods, we identify an accessory genome signature associated with dissemination and define the individual plasmids and genes that make up this signature. Strains within the RST1/WGS A subgroup, particularly a subset marked by the OspC type A genotype, are associated with increased rates of dissemination. OspC type A strains possess a unique constellation of strongly linked genetic changes including the presence of lp56 and lp28-1 plasmids and a cluster of genes that may contribute to their enhanced virulence compared to other genotypes. The patterns of OspC type A strains typify a broader paradigm across Bbss isolates, in which genetic structure is defined by correlated groups of strain-variable genes located predominantly on plasmids, particularly for expression of surface-exposed lipoproteins. These clusters of genes are inherited in blocks through strain-specific patterns of plasmid occupancy and are associated with the probability of invasive infection.