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

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 repor...

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Autores principales: Lemieux, Jacob E., Huang, Weihua, Hill, Nathan, Cerar, Tjasa, Freimark, Lisa, Hernandez, Sergio, Luban, Matteo, Maraspin, Vera, Bogovič, Petra, Ogrinc, Katarina, Ruzič-Sabljič, Eva, Lapierre, Pascal, Lasek-Nesselquist, Erica, Singh, Navjot, Iyer, Radha, Liveris, Dionysios, Reed, Kurt D., Leong, John M., Branda, John A., Steere, Allen C., Wormser, Gary P., Strle, Franc, Sabeti, Pardis C., Schwartz, Ira, Strle, Klemen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470944/
https://www.ncbi.nlm.nih.gov/pubmed/37651316
http://dx.doi.org/10.1371/journal.ppat.1011243
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author Lemieux, Jacob E.
Huang, Weihua
Hill, Nathan
Cerar, Tjasa
Freimark, Lisa
Hernandez, Sergio
Luban, Matteo
Maraspin, Vera
Bogovič, Petra
Ogrinc, Katarina
Ruzič-Sabljič, Eva
Lapierre, Pascal
Lasek-Nesselquist, Erica
Singh, Navjot
Iyer, Radha
Liveris, Dionysios
Reed, Kurt D.
Leong, John M.
Branda, John A.
Steere, Allen C.
Wormser, Gary P.
Strle, Franc
Sabeti, Pardis C.
Schwartz, Ira
Strle, Klemen
author_facet Lemieux, Jacob E.
Huang, Weihua
Hill, Nathan
Cerar, Tjasa
Freimark, Lisa
Hernandez, Sergio
Luban, Matteo
Maraspin, Vera
Bogovič, Petra
Ogrinc, Katarina
Ruzič-Sabljič, Eva
Lapierre, Pascal
Lasek-Nesselquist, Erica
Singh, Navjot
Iyer, Radha
Liveris, Dionysios
Reed, Kurt D.
Leong, John M.
Branda, John A.
Steere, Allen C.
Wormser, Gary P.
Strle, Franc
Sabeti, Pardis C.
Schwartz, Ira
Strle, Klemen
author_sort Lemieux, Jacob E.
collection PubMed
description 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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spelling pubmed-104709442023-09-01 Whole genome sequencing of human Borrelia burgdorferi isolates reveals linked blocks of accessory genome elements located on plasmids and associated with human dissemination Lemieux, Jacob E. Huang, Weihua Hill, Nathan Cerar, Tjasa Freimark, Lisa Hernandez, Sergio Luban, Matteo Maraspin, Vera Bogovič, Petra Ogrinc, Katarina Ruzič-Sabljič, Eva Lapierre, Pascal Lasek-Nesselquist, Erica Singh, Navjot Iyer, Radha Liveris, Dionysios Reed, Kurt D. Leong, John M. Branda, John A. Steere, Allen C. Wormser, Gary P. Strle, Franc Sabeti, Pardis C. Schwartz, Ira Strle, Klemen PLoS Pathog Research Article 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. Public Library of Science 2023-08-31 /pmc/articles/PMC10470944/ /pubmed/37651316 http://dx.doi.org/10.1371/journal.ppat.1011243 Text en © 2023 Lemieux et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lemieux, Jacob E.
Huang, Weihua
Hill, Nathan
Cerar, Tjasa
Freimark, Lisa
Hernandez, Sergio
Luban, Matteo
Maraspin, Vera
Bogovič, Petra
Ogrinc, Katarina
Ruzič-Sabljič, Eva
Lapierre, Pascal
Lasek-Nesselquist, Erica
Singh, Navjot
Iyer, Radha
Liveris, Dionysios
Reed, Kurt D.
Leong, John M.
Branda, John A.
Steere, Allen C.
Wormser, Gary P.
Strle, Franc
Sabeti, Pardis C.
Schwartz, Ira
Strle, Klemen
Whole genome sequencing of human Borrelia burgdorferi isolates reveals linked blocks of accessory genome elements located on plasmids and associated with human dissemination
title Whole genome sequencing of human Borrelia burgdorferi isolates reveals linked blocks of accessory genome elements located on plasmids and associated with human dissemination
title_full Whole genome sequencing of human Borrelia burgdorferi isolates reveals linked blocks of accessory genome elements located on plasmids and associated with human dissemination
title_fullStr Whole genome sequencing of human Borrelia burgdorferi isolates reveals linked blocks of accessory genome elements located on plasmids and associated with human dissemination
title_full_unstemmed Whole genome sequencing of human Borrelia burgdorferi isolates reveals linked blocks of accessory genome elements located on plasmids and associated with human dissemination
title_short Whole genome sequencing of human Borrelia burgdorferi isolates reveals linked blocks of accessory genome elements located on plasmids and associated with human dissemination
title_sort whole genome sequencing of human borrelia burgdorferi isolates reveals linked blocks of accessory genome elements located on plasmids and associated with human dissemination
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470944/
https://www.ncbi.nlm.nih.gov/pubmed/37651316
http://dx.doi.org/10.1371/journal.ppat.1011243
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