Whole genome sequencing of human Borrelia burgdorferi isolates reveals linked blocks of accessory genome elements located on plasmids and associated with human dissemination.

IF 6.7 1区 医学 Q1 Immunology and Microbiology
PLoS Pathogens Pub Date : 2023-08-31 eCollection Date: 2023-08-01 DOI:10.1371/journal.ppat.1011243
Jacob E Lemieux, Weihua Huang, Nathan Hill, Tjasa Cerar, Lisa Freimark, Sergio Hernandez, Matteo Luban, Vera Maraspin, Petra Bogovič, Katarina Ogrinc, Eva Ruzič-Sabljič, Pascal Lapierre, Erica Lasek-Nesselquist, Navjot Singh, Radha Iyer, Dionysios Liveris, Kurt D Reed, John M Leong, John A Branda, Allen C Steere, Gary P Wormser, Franc Strle, Pardis C Sabeti, Ira Schwartz, Klemen Strle
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引用次数: 0

Abstract

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 B. burgdorferi (Bb) isolates derived from patients in the Eastern and Midwestern US and Central Europe. We develop a WGS-based classification of Bb isolates, confirm and extend the findings of previous single- and multi-locus typing systems, define the plasmid profiles of human-infectious Bb isolates, annotate the core and strain-variable surface lipoproteome, and identify loci associated with disseminated infection. A core genome consisting of ~900 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 in humans 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, have increased rates of dissemination in humans. OspC type A strains possess a unique set of strongly linked genetic elements 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. These features of OspC type A strains reflect a broader paradigm across Bb isolates, in which near-clonal genotypes are defined by strain-specific clusters of linked genetic elements, particularly those encoding surface-exposed lipoproteins. These clusters of genes are maintained by strain-specific patterns of plasmid occupancy and are associated with the probability of invasive infection.

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对人伯氏疏螺旋体分离株的全基因组测序揭示了位于质粒上并与人类传播相关的辅助基因组元件的连接块。
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而异,但这些关联背后的微生物遗传因素尚不清楚。在此,我们报道了299个来自美国东部、中西部和中欧患者的伯氏双歧杆菌(Bb)分离株的全基因组序列(WGS)和分析。我们开发了一种基于WGS的Bb分离株分类,证实并扩展了以前的单基因座和多基因座分型系统的发现,定义了人类传染性Bb分离物的质粒图谱,注释了核心和菌株可变表面脂蛋白组,并鉴定了与播散性感染相关的基因座。在几乎所有分离株中都发现了一个由~900个开放阅读框组成的核心基因组和一组由lp17、lp25、lp36、lp28-3、lp28-4、lp54和cp26组成的核心质粒。菌株可变(附属)质粒和基因与系统发育密切相关。使用遗传关联研究方法,我们确定了与人类传播相关的辅助基因组特征,并定义了构成该特征的单个质粒和基因。RST1/WGS A亚群内的菌株,特别是以OspC A型基因型为标志的亚群,在人类中的传播率增加。OspC A型菌株具有一组独特的强连锁遗传元件,包括lp56和lp28-1质粒的存在,以及与其他基因型相比可能有助于增强毒力的基因簇。OspC A型菌株的这些特征反映了Bb分离株中更广泛的模式,其中近克隆基因型由连锁遗传元件的菌株特异性簇定义,特别是编码表面暴露的脂蛋白的那些。这些基因簇由质粒占据的菌株特异性模式维持,并与侵袭性感染的概率有关。
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来源期刊
PLoS Pathogens
PLoS Pathogens 生物-病毒学
CiteScore
11.40
自引率
3.00%
发文量
598
审稿时长
2 months
期刊介绍: Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.
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