NYMC Faculty Publications

Whole Genome Sequencing of Human Borrelia Burgdorferi Isolates Reveals Linked Blocks of Accessory Genome Elements Located on Plasmids and Associated With Human Dissemination

Authors

Jacob E. Lemieux, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Weihua Huang, New York Medical College, Valhalla, New York, United States of America.
Nathan Hill, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Tjasa Cerar, University of Ljubljana, Ljubljana, Slovenia.
Lisa Freimark, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
Sergio Hernandez, Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
Matteo Luban, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Vera Maraspin, University Medical Center Ljubljana, Ljubljana, Slovenia.
Petra Bogovič, University Medical Center Ljubljana, Ljubljana, Slovenia.
Katarina Ogrinc, University Medical Center Ljubljana, Ljubljana, Slovenia.
Eva Ruzič-Sabljič, University of Ljubljana, Ljubljana, Slovenia.
Pascal Lapierre, Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
Erica Lasek-Nesselquist, Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
Navjot Singh, Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
Radha Iyer, New York Medical College, Valhalla, New York, United States of America.
Dionysios Liveris, New York Medical College, Valhalla, New York, United States of America.
Kurt D. Reed, University of Wisconsin, Madison, Wisconsin, United States of America.
John M. Leong, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
John A. Branda, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Allen C. Steere, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Gary P. Wormser, New York Medical College, Valhalla, New York, United States of America.
Franc Strle, University Medical Center Ljubljana, Ljubljana, Slovenia.
Pardis C. Sabeti, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Ira Schwartz, New York Medical College, Valhalla, New York, United States of America.
Klemen Strle, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.

Author Type(s)

Faculty

Journal Title

PLOS Pathogens

First Page

e1011243

Document Type

Article

Publication Date

8-1-2023

Department

Pathology, Microbiology and Immunology

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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