Multipartite Genome of Lyme Disease Borrelia: Structure, Variation and Prophages

Abstract

All members of the Borrelia genus that have been examined harbour a linear chromosome that is about 900 kbp in length, as well as a plethora of both linear and circular plasmids in the 5-220 kbp size range. Genome sequences for 27 Lyme disease Borrelia isolates have been determined since the elucidation of the B. burgdorferi B31 genome sequence in 1997. The chromosomes, which carry the vast majority of the housekeeping genes, appear to be very constant in gene content and organization across all Lyme disease Borrelia species. The content of the plasmids, which carry most of the genes that encode the differentially expressed surface proteins that interact with the spirochete's arthropod and vertebrate hosts, is much more variable. Lyme disease Borrelia isolates carry between 7-21 different plasmids, ranging in size from 5-84 kbp. All strains analyzed to date harbor three plasmids, cp26, lp54 and lp17. The plasmids are unusual, as compared to most bacterial plasmids, in that they contain many paralogous sequences, a large number of pseudogenes, and, in some cases, essential genes. In addition, a number of the plasmids have features indicating that they are prophages. Numerous methods have been developed for Lyme disease Borrelia strain typing. These have proven valuable for clinical and epidemiological studies, as well as phylogenomic and population genetic analyses. Increasingly, these approaches have been displaced by whole genome sequencing techniques. Some correlations between genome content and pathogenicity have been deduced, and comparative whole genome analyses promise future progress in this arena. caister.com/cimb 409 Curr. Issues Mol. Biol. Vol. 42 Curr. Issues Mol. Biol. 42: 409-454. caister.com/cimb Multipartite Genome of Borrelia Schwartz et al.

The evolving story of Borrelia burgdorferi sensu lato transmission in Europe

“…In fact, spirochetes developed numerous strategies to overcome the innate and the adaptive immune response to prevent elimination by the host’s immune system (Hyde 2017 ; Kurokawa et al 2020 ; Lin et al 2020 ; Anderson and Brissette 2021 ). The ~1780 genes in the genome of B. burgdorferi s.s. strain B31 M1 are located on a single linear chromosome (910 kbp) and ~21 linear and circular plasmids (Fraser et al 1997 ; Casjens et al 2000 ; Pal and Fikrig 2003 ; Schwartz et al 2021 ) and can be regulated to respond to environmental changes. Spirochetes are capable to alter the regulation of multiple genes involved in cell metabolism, motility, interaction with host- and tick-derived molecules, and thereby impacting responses of their vectors and hosts.…”

Recent Progress in Lyme Disease and Remaining Challenges

“…Bb has one of the most complex genomes of any bacteria characterized to-date [reviewed in (143)]. Bb contains a single linear chromosome of ∼900 k base pairs (bp) with between 7 and 21 different plasmids, ranging in size from 5 to 84 kbp as reviewed from the genome sequences for 27 Bb isolates determined since the elucidation of the Bb B31 genome sequence in 1997 (144).…”

“…In the Bb genome, the conserved linear chromosome encodes most housekeeping genes, while the variable set of linear and circular plasmids encodes most of the outer membrane lipoproteins (149)(150)(151). Three plasmids, cp26, lp17, and lp54, are conserved across sequenced isolates of Bb to-date [reviewed in (143)]. The content and number of the plasmids however appear much more variable with some loss of these once Bb is in vitro cultured for an extended period of time.…”

Large-Scale Sequencing of Borreliaceae for the Construction of Pan-Genomic-Based Diagnostics

“…The distribution of these virulence genes can be on either the small linear or circular replicons. To date, the Borrelial linear plasmids (lp) have been suggested to contain fewer functional genes and are laced with pseudogenes [ 247 , 248 , 249 ]. In contrast, the circular plasmids hold more coding genes [ 250 ].…”

“…The smaller episome, lp17, differs from lp54 by containing genes for homologous proteins with unknown functions and an end with high homology to other linear Borrleiella replicons. Lp17 also varies greatly among different Borreliaceae species, amounting to 16 variants identified to date [ 247 ]. Lastly, cp26 is highly syntenic and contains genes that encode key metabolic and nutrient import proteins.…”