Whole Genome Sequence and Comparative Genomics of the Novel Lyme Borreliosis Causing Pathogen, Borrelia mayonii

Abstract

Borrelia mayonii, a Borrelia burgdorferi sensu lato (Bbsl) genospecies, was recently identified as a cause of Lyme borreliosis (LB) among patients from the upper midwestern United States. By microscopy and PCR, spirochete/genome loads in infected patients were estimated at 105 to 106 per milliliter of blood. Here, we present the full chromosome and plasmid sequences of two B. mayonii isolates, MN14-1420 and MN14-1539, cultured from blood of two of these patients. Whole genome sequencing and assembly was conducted using PacBio long read sequencing (Pacific Biosciences RSII instrument) followed by hierarchical genome-assembly process (HGAP). The B. mayonii genome is ~1.31 Mbp in size (26.9% average GC content) and is comprised of a linear chromosome, 8 linear and 7 circular plasmids. Consistent with its taxonomic designation as a new Bbsl genospecies, the B. mayonii linear chromosome shares only 93.83% average nucleotide identity with other genospecies. Both B. mayonii genomes contain plasmids similar to B. burgdorferi sensu stricto lp54, lp36, lp28-3, lp28-4, lp25, lp17, lp5, 5 cp32s, cp26, and cp9. The vls locus present on lp28-10 of B. mayonii MN14-1420 is remarkably long, being comprised of 24 silent vls cassettes. Genetic differences between the two B. mayonii genomes are limited and include 15 single nucleotide variations as well as 7 fewer silent vls cassettes and a lack of the lp5 plasmid in MN14-1539. Notably, 68 homologs to proteins present in B. burgdorferi sensu stricto appear to be lacking from the B. mayonii genomes. These include the complement inhibitor, CspZ (BB_H06), the fibronectin binding protein, BB_K32, as well as multiple lipoproteins and proteins of unknown function. This study shows the utility of long read sequencing for full genome assembly of Bbsl genomes, identifies putative genome regions of B. mayonii that may be linked to clinical manifestation or tissue tropism, and provides a valuable resource for pathogenicity, diagnostic and vaccine studies.

Comprehensive Spatial Analysis of the Borrelia burgdorferi Lipoproteome Reveals a Compartmentalization Bias toward the Bacterial Surface

“…Placing our lipoproteome localization data into the context of genome-and proteome-wide studies may facilitate the identification of additional diagnostic targets and vaccine candidates. The proteomic localization data presented here also provide a predictive framework for proteomic studies of host-pathogen interfaces and envelope structures of other members of the ever-expanding Borrelia genus, including the relapsing fever spirochete Borrelia miyamotoi (136,137) and the recently described North American Lyme disease spirochete Borrelia mayonii (138,139).…”

Borrelia lanei sp. nov. extends the diversity of Borrelia species in California

“…The closest-related genospecies of the B. burgdorferi s.l. species complex were Borrelia species from North America with B. mayonii, a human pathogenic genospecies recently discovered in the Midwest of the USA [11,12], showing the lowest genetic distance to type strain CA28-91 T (0.040, which equals 96 % similarity) followed by B. burgdorferi s. s. strains Z41293 and B31 (0.042 and 0.045, respectively) and B. americana (0.049) (Fig. 1 and Table S1, available in the online Supplementary Material).…”

Studies that report unexpected positive blood cultures for Lyme borrelia – are they valid?

“…The authors did state that none of the patients had received antibiotic therapy within the 4 weeks prior to collection of the blood samples. Investigators from the CDC analyzed genetic sequencing data of the isolates said to be recovered using this technique and found that most were not B. burgdorferi sensu stricto [17,18], making the results highly implausible, as infection with Lyme borrelia species other than sensu stricto has not been documented in North America, aside from a very small number of infections due to B. mayonii [19]. The findings of this study were most consistent with laboratory contamination [17,18].…”