| Autor: |
Lemieux JE; Massachusetts General Hospital, Harvard Medical School.; Broad Institute of MIT and Harvard., Huang W; New York Medical College.; East Carolina University., Hill N; Massachusetts General Hospital, Harvard Medical School.; Broad Institute of MIT and Harvard., Cerar T; University of Ljubljana., Freimark L; Broad Institute of MIT and Harvard., Hernandez S; Wadsworth Center., Luban M; Massachusetts General Hospital, Harvard Medical School.; Broad Institute of MIT and Harvard., Maraspin V; University Medical Center Ljubljana., Bogovic P; University Medical Center Ljubljana., Ogrinc K; University Medical Center Ljubljana., Ruzic-Sabljic E; University of Ljubljana., Lapierre P; Wadsworth Center., Lasek-Nesselquist E; Wadsworth Center., Singh N; Wadsworth Center., Iyer R; New York Medical College., Liveris D; New York Medical College., Reed KD; University of Wisconsin., Leong JM; Tufts University, Department of Molecular Biology and Microbiology., Branda JA; Massachusetts General Hospital, Harvard Medical School., Steere AC; Massachusetts General Hospital, Harvard Medical School., Wormser GP; New York Medical College., Strle F; University Medical Center Ljubljana., Sabeti PC; Massachusetts General Hospital, Harvard Medical School.; Broad Institute of MIT and Harvard.; Harvard University.; Harvard T.H.Chan School of Public Health., Schwartz I; New York Medical College., Strle K; Massachusetts General Hospital, Harvard Medical School.; Wadsworth Center. |
| Abstrakt: |
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. |
