Genetics of Borrelia burgdorferi

Abstract

The spirochetes in the Borrelia burgdorferi sensu lato genospecies group cycle in nature between tick vectors and vertebrate hosts. The current assemblage of B. burgdorferi sensu lato, of which three species cause Lyme disease in humans, originated from a rapid species radiation that occurred near the origin of the clade. All of these species share a unique genome structure that is highly segmented and predominantly composed of linear replicons. One of the circular plasmids is a prophage that exists as several isoforms in each cell and can be transduced to other cells, likely contributing to an otherwise relatively anemic level of horizontal gene transfer, which nevertheless appears to be adequate to permit strong natural selection and adaptation in populations of B. burgdorferi. Although the molecular genetic toolbox is meager, several antibiotic-resistant mutants have been isolated, and the resistance alleles, as well as some exogenous genes, have been fashioned into markers to dissect gene function. Genetic studies have probed the role of the outer membrane lipoprotein OspC, which is maintained in nature by multiple niche polymorphisms and negative frequency-dependent selection. One of the most intriguing genetic systems in B. burgdorferi is vls recombination, which generates antigenic variation during infection of mammalian hosts.

Figure 1

Live Borrelia burgdorferi sensu stricto stained with wheat germ agglutinin Alexa Fluor^® 594.

Figure 2

Bayesian phylogenies of Borrelia burgdorferi sensu lato; triangles represent the diversity within genospecies. The rapid burst of speciation that occurred early in the evolutionary history of the group can be inferred from both the (a) chromosome sequences and (b) the multilocus phylogenies. Nodes marked with asterisks are supported by posterior probabilities of more than 0.8 (∗), 0.9 (∗∗), and 0.95 (∗∗∗). Figure adapted from Morlon et al. (112).

Figure 3

Enzootic cycle of Borrelia burgdorferi. Spirochetes are acquired when Ixodes spp. larvae feed on their first vertebrate host, usually a small mammal or bird. Larvae then molt to nymphs, which transmit the spirochetes when they feed on a second vertebrate host. Nymphs molt to adults, which feed on a third vertebrate host. All three stages of ticks feed on humans, which are thought to be incidental hosts, but B. burgdorferi transmission by nymphs is considered to cause most cases of Lyme disease.

Figure 4

Electron micrograph of negatively stained Borrelia burgdorferi (a) before and (b) after electroporation. Following electroporation, B. burgdorferi have darkly stained regions, as visualized by transmission electron microscopy, that are thought to be transient pores through which the DNA enters (or leaves) the cell. Reprinted with permission from Samuels & Garon (145).

Figure 5

Bacteriophage ϕBB-1 of Borrelia burgdorferi. Virions were recovered from the supernatant of a culture that had been treated with 1-methyl-3-nitrosonitroguanidine. The phage particles were negatively stained with phosphotungstic acid and observed by transmission electron microscopy. Reproduced with permission from Eggers et al. (51).