Whole genome sequencing ofBorrelia burgdorferiisolates reveals linked clusters of plasmid-borne accessory genome elements associated with virulence Article Swipe
Jacob E. Lemieux
,
Weihua Huang
,
Nathan Hill
,
Tjaša Cerar
,
Lisa M. Freimark
,
Sergio Hernandez
,
Matteo Luban
,
Vera Maraspin
,
Petra Bogovič
,
Katarina Ogrinc
,
Eva Ružić‐Sabljić
,
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
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.02.26.530159
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1101/2023.02.26.530159
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.
Related Topics
Concepts
Virulence
Genome
Plasmid
Biology
Borrelia burgdorferi
Whole genome sequencing
Genetics
Microbiology
Virology
Gene
Antibody
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2023.02.26.530159
- https://www.biorxiv.org/content/biorxiv/early/2023/02/27/2023.02.26.530159.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 88
- Related Works
- 10
- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4322489234Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2023.02.26.530159Digital Object Identifier
- Title
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Whole genome sequencing ofBorrelia burgdorferiisolates reveals linked clusters of plasmid-borne accessory genome elements associated with virulenceWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-02-27Full publication date if available
- Authors
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Jacob E. Lemieux, Weihua Huang, Nathan Hill, Tjaša Cerar, Lisa M. Freimark, Sergio Hernandez, Matteo Luban, Vera Maraspin, Petra Bogovič, Katarina Ogrinc, Eva Ružić‐Sabljić, 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 StrleList of authors in order
- Landing page
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https://doi.org/10.1101/2023.02.26.530159Publisher landing page
- PDF URL
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https://www.biorxiv.org/content/biorxiv/early/2023/02/27/2023.02.26.530159.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2023/02/27/2023.02.26.530159.full.pdfDirect OA link when available
- Concepts
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Virulence, Genome, Plasmid, Biology, Borrelia burgdorferi, Whole genome sequencing, Genetics, Microbiology, Virology, Gene, AntibodyTop concepts (fields/topics) attached by OpenAlex
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10Other works algorithmically related by OpenAlex
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