Lyme disease is the commonest vector-borne illness in North America and Europe. The scientific manifestations of Lyme disease fluctuate primarily based on the genospecies of the infecting Borrelia burgdorferi spirochete, however the microbial genetic parts underlying these associations aren’t identified. Right here, we report the entire genome sequence (WGS) and evaluation of 299 B. burgdorferi (Bb) isolates derived from sufferers within the Jap and Midwestern US and Central Europe. We develop a WGS-based classification of Bb isolates, affirm and lengthen the findings of earlier single- and multi-locus typing techniques, outline the plasmid profiles of human-infectious Bb isolates, annotate the core and strain-variable floor lipoproteome, and determine loci related to disseminated an infection. A core genome consisting of ~900 open studying frames and a core set of plasmids consisting of lp17, lp25, lp36, lp28-3, lp28-4, lp54, and cp26 are present in almost all isolates. Pressure-variable (accent) plasmids and genes correlate strongly with phylogeny. Utilizing genetic affiliation examine strategies, we determine an adjunct genome signature related to dissemination in people and outline the person plasmids and genes that make up this signature. Strains throughout the RST1/WGS A subgroup, significantly a subset marked by the OspC sort A genotype, have elevated charges of dissemination in people. OspC sort A strains possess a novel set of strongly linked genetic parts together with the presence of lp56 and lp28-1 plasmids and a cluster of genes which will contribute to their enhanced virulence in comparison with different genotypes. These options of OspC sort A strains replicate a broader paradigm throughout Bb isolates, by which near-clonal genotypes are outlined by strain-specific clusters of linked genetic parts, significantly these encoding surface-exposed lipoproteins. These clusters of genes are maintained by strain-specific patterns of plasmid occupancy and are related to the likelihood of invasive an infection.