Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

Abstract

Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33–40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi ∼900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short ≤20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.

Lyme disease and relapsing feverBorreliaelongate through zones of peptidoglycan synthesis that mark division sites of daughter cells

“…B. burgdorferi sensu stricto is an umbrella term used to define all strains that are closely related to the type strain B31 MI (18). These strains exhibit genotypic variability (19,20). Furthermore, under our laboratory conditions, we observed differences in cell length distribution among B. burgdorferi strains (Fig.…”

A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity

“…Borreliosis is caused by a variety of species of Borrelia burgdorferi sensu lato complex, some of which show distinct differences in their pathogenic properties in the human host (5). Borrelia species have a highly complex genomic structure and genetic variation may account for a large proportion of the variability of pathogenicity (6). However, pathogens are not only depending on their own fitness for a successful establishment of infection, but also on the genetic makeup of their hosts.…”

Hairpin Telomere Resolvases

“…Similarly, two rounds of fusion/deletion of the B31 chromosome, first with an lp28-1 and subsequently with lp28-5, would have generated the JD1 chromosome. The sequence relatedness of the chromosomes and plasmids shown were reported by references 44,46,47,48. This figure is slightly modified from reference 46. doi:10.1128 /microbiolspec.MDNA3-0023-2014.f5 fusions would be frozen in time and available to participate in subsequent telomere fusion and recombination events in the future.…”

“…Another unusual feature in the genus Borrelia is the ongoing genome plasticity in the telomeric and subtelomeric regions of the linear chromosome and plasmids (44,46,47,48,49). Extensions of linear plasmid sequences can be found on the ends of some chromosomes and other linear plasmids (Fig.…”

“…In addition, the subterminal regions of many linear plasmids are a patchwork of repeated sequences found on other linear plasmids. Sequencing of recombination breakpoints indicates that these genome rearrangements result from nonhomologous recombination events, however, no molecular mechanism for their generation was proposed (44,46,47,48). A hint as to a possible molecular mechanism comes from the demonstration that telomere resolution by ResT is a reversible reaction (15).…”