Out of the Woods: the Remarkable Genomes of the Genus Borrelia

In this issue of the Journal of Bacteriology, Casjens et al. (5) report the sequencing and annotation of four genomes from the Lyme borreliosis group: Borrelia afzelii isolates PKo and ACA-1 and Borrelia garinii strains PBr and Far04. The first three strains were isolated from a human early Lyme borreliosis lesion (erythema migrans) in Germany, a late skin lesion (acrodermatitis chronica atrophicans [ACA]) in Sweden, and cerebrospinal fluid from a neuroborreliosis patient in Germany. The fourth is an avian isolate from a puffin in the Faroe Islands, Denmark. With this article and two other Genome Announcements published earlier this year (4, 14), this group has reported the genome sequences of 18 Lyme disease Borrelia isolates in 2011. (Genome Announcements, initiated by the Journal of Bacteriology in 2007, provide a convenient and popular mechanism for informing the scientific community about newly completed sequences. As of September 2011, 388 Genome Announcements have been published, including 293 in the first 9 months of 2011.) The goal of this ambitious project was to provide the information needed for comparative genomics among Borrelia species and strains, thereby permitting the identification of shared and unique genetic elements related to the biologic and pathogenic properties of this unique group of organisms. Combined with the inaugural sequencing of the B. burgdorferi B31 genome in 1997 (2, 9) and additional published and unpublished sequences, there are currently complete or partial sequences for 24 Lyme borreliosis and 4 relapsing fever Borrelia genomes. This expansion is in keeping with the overall increase in prokaryotic genome sequences, which at the time of this writing stands at 1,760 complete microbial genomes and 5,230 genome projects in progress (http://www.ncbi.nlm.nih.gov/genomes /lproks.cgi). The availability of multiple genome sequences has brought Borrelia species “out of the woods” by providing a wealth of information on molecular evolution that microbiologists are just now beginning to unravel. Members of the genus Borrelia are obligate extracellular spirochetes that alternate between two vastly different environments: vertebrate tissue (primarily of mammals and birds) and the midgut of arthropods (ticks or lice). The borreliae can be divided into two groups: those causing Lyme borreliosis and those giving rise to relapsing fever. Except in the case of Borrelia recurrentis, the cause of louse-borne epidemic relapsing fever, humans are an accidental, dead-end host of borrelial infection and are not involved the transmission cycle. Lyme disease Borrelia organisms are subdivided into 10 species and two proposed species. Only four of these commonly cause human disease: B. burgdorferi, B. garinii, B. afzelii, and B. bavariensis. Relapsing fever Borrelia consists of 22 species, which differ in terms of both the transmitting arthropod and geographic distribution. The classification of Lyme disease Borrelia has been a case of “lumpers” versus “splitters,” and in this instance the splitters won the battle. This process began with classic genetic and immunoreactivity comparison studies performed by Baranton et al. (1), who found that European human Lyme disease isolates could be subdivided into three subgroups: B. burgdorferi and two other groups that later became the species B. afzelii and B. garinii. Further additions have resulted in the current total of 10 species and 2 proposed species. Within Borrelia species, additional subdivisions exist based on rRNA gene intergenic spacer and outer surface protein C (ospC) divergence, and, most recently, multilocus sequence analysis. This splitting is clinically relevant, because disease manifestations correlate to some extent with species and their subgroups. For example, B. burgdorferi tends to cause arthritic symptoms, B. garinii is more strongly associated with neurologic signs, and B. afzelii is linked to the late skin lesion ACA. B. burgdorferi subgroups in North America vary in their ability to be disseminated in humans and other mammals, as demonstrated by isolation of organisms from blood as well as from skin biopsy specimens. The complexity of Lyme borreliosis, including the dramatic regulation of gene expression that occurs in the transitions between vertebrate and arthropod hosts, was addressed in detail in a recent monograph (13). Despite a close genetic relationship with Lyme disease borreliae, the relapsing fever borreliae have quite different biological properties and patterns of pathogenesis (Table 1). Most endemic relapsing fever species are specifically “paired” with particular species of soft-bodied, fast-feeding ticks of the genus Ornithodoros; however, the epidemic relapsing fever species B. recurrentis is carried by human lice. Infection of humans is characterized by phases of high bacteremia (up to 10 per ml of blood) accompanied by intense fever and other constitutional symptoms. The Borrelia genomes are unusual in their conformation, consisting of a single linear chromosome and up to 24 linear and circular plasmids. The chromosomes, ranging in size from 904 kb to 932 kb, exhibit a high degree of synteny in terms of * Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, P.O. Box 20708, Houston, TX 77225-0708. Phone: (713) 500-5338. Fax: (713) 500-0730. E-mail: Steven.J.Norris@uth.tmc.edu. Published ahead of print on 14 October 2011.