Microbiology of Lyme disease
- Alan G Barbour, MD
Alan G Barbour, MD
- Professor of Medicine and Microbiology & Molecular Genetics
- University of California Irvine School of Medicine
Lyme disease is the most common tick-borne disease in the United States, Canada, and Europe [1,2]. It is a bacterial infection caused by members of the Borrelia species, Borrelia burgdorferi in North America, and primarily by Borrelia afzelii and Borrelia garinii in Europe and Asia. The reservoirs in nature are several species of small mammals and birds. Humans acquire the infection not from direct contact with these vertebrates, but from the bite of an infected tick of the genus Ixodes. The infection begins in the skin at the site of the tick bite. From there, the spirochetes may disseminate in the blood to other tissues and organs. The usual manifestations of Lyme disease involve the skin, joints, heart, and nervous system.
In the early 20th century, erythema migrans and Bannwarth’s syndrome, which are now known to be skin and neurologic manifestations of Lyme borreliosis, were described in Europe . Lyme disease was first described in North America in 1977 as "Lyme arthritis" , and the etiologic agent was identified in 1982 .
The microbiology of Lyme disease will be reviewed here. Issues related to immunopathogenesis, epidemiology, prevention, clinical manifestations, diagnosis, and therapy of Lyme disease are discussed separately. (See "Epidemiology of Lyme disease" and "Immunopathogenesis of Lyme disease" and "Prevention of Lyme disease" and "Evaluation of a tick bite for possible Lyme disease" and "Clinical manifestations of Lyme disease in adults" and "Lyme disease: Clinical manifestations in children" and "Treatment of Lyme disease".)
CLASSIFICATION AND GENOME
The members of Borrelia species are spirochetes, which are motile, spiral, or wavy bacteria that are only distantly related to gram-negative and gram-positive pathogens. The genomes of B. burgdorferi, B. afzelii, and B. garinii comprise small linear chromosomes of approximately 1000 kb, and 17 to 21 linear and circular plasmids totaling another 400 to 500 kb [6-8].
Spirochetes have two cellular membranes like gram-negative bacteria, but their flagella, the organelles of motility, are uniquely located between in the inner and outer membrane rather than on the surface. B. burgdorferi is 8 to 30 microns in length and about 0.2 microns in width. Their narrowness accounts for the inability to see unstained or Gram stained cells by standard light microscopy.
- Steere AC, Coburn J, Glickstein L. The emergence of Lyme disease. J Clin Invest 2004; 113:1093.
- Stanek G, Wormser GP, Gray J, Strle F. Lyme borreliosis. Lancet 2012; 379:461.
- Stanek G, Pletschette M, Flamm H, et al. European Lyme borreliosis. Ann N Y Acad Sci 1988; 539:274.
- Steere AC, Malawista SE, Snydman DR, et al. Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities. Arthritis Rheum 1977; 20:7.
- Burgdorfer W, Barbour AG, Hayes SF, et al. Lyme disease-a tick-borne spirochetosis? Science 1982; 216:1317.
- Fraser CM, Casjens S, Huang WM, et al. Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 1997; 390:580.
- Ferdows MS, Barbour AG. Megabase-sized linear DNA in the bacterium Borrelia burgdorferi, the Lyme disease agent. Proc Natl Acad Sci U S A 1989; 86:5969.
- Casjens S, Palmer N, van Vugt R, et al. A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi. Mol Microbiol 2000; 35:490.
- Bergström S, Bundoc VG, Barbour AG. Molecular analysis of linear plasmid-encoded major surface proteins, OspA and OspB, of the Lyme disease spirochaete Borrelia burgdorferi. Mol Microbiol 1989; 3:479.
- Padula SJ, Dias F, Sampieri A, et al. Use of recombinant OspC from Borrelia burgdorferi for serodiagnosis of early Lyme disease. J Clin Microbiol 1994; 32:1733.
- Guo BP, Norris SJ, Rosenberg LC, Höök M. Adherence of Borrelia burgdorferi to the proteoglycan decorin. Infect Immun 1995; 63:3467.
- Zhang JR, Hardham JM, Barbour AG, Norris SJ. Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes. Cell 1997; 89:275.
- Schwan TG, Piesman J, Golde WT, et al. Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proc Natl Acad Sci U S A 1995; 92:2909.
- Margolis N, Rosa PA. Regulation of expression of major outer surface proteins in Borrelia burgdorferi. Infect Immun 1993; 61:2207.
- de Silva AM, Fikrig E. Arthropod- and host-specific gene expression by Borrelia burgdorferi. J Clin Invest 1997; 99:377.
- Tilly K, Bestor A, Dulebohn DP, Rosa PA. OspC-independent infection and dissemination by host-adapted Borrelia burgdorferi. Infect Immun 2009; 77:2672.
- Tilly K, Krum JG, Bestor A, et al. Borrelia burgdorferi OspC protein required exclusively in a crucial early stage of mammalian infection. Infect Immun 2006; 74:3554.
- Takayama K, Rothenberg RJ, Barbour AG. Absence of lipopolysaccharide in the Lyme disease spirochete, Borrelia burgdorferi. Infect Immun 1987; 55:2311.
- Hirschfeld M, Kirschning CJ, Schwandner R, et al. Cutting edge: inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2. J Immunol 1999; 163:2382.
- Hoen AG, Margos G, Bent SJ, et al. Phylogeography of Borrelia burgdorferi in the eastern United States reflects multiple independent Lyme disease emergence events. Proc Natl Acad Sci U S A 2009; 106:15013.
- Girard YA, Travinsky B, Schotthoefer A, et al. Population structure of the lyme borreliosis spirochete Borrelia burgdorferi in the western black-legged tick (Ixodes pacificus) in Northern California. Appl Environ Microbiol 2009; 75:7243.
- Brown RN, Peot MA, Lane RS. Sylvatic maintenance of Borrelia burgdorferi (Spirochaetales) in Northern California: untangling the web of transmission. J Med Entomol 2006; 43:743.
- Baranton G, Postic D, Saint Girons I, et al. Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461 associated with Lyme borreliosis. Int J Syst Bacteriol 1992; 42:378.
- Baranton G, De Martino SJ. Borrelia burgdorferi sensu lato diversity and its influence on pathogenicity in humans. Curr Probl Dermatol 2009; 37:1.
- Bunikis J, Garpmo U, Tsao J, et al. Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe. Microbiology 2004; 150:1741.
- Chao LL, Chen YJ, Shih CM. First isolation and molecular identification of Borrelia burgdorferi sensu stricto and Borrelia afzelii from skin biopsies of patients in Taiwan. Int J Infect Dis 2011; 15:e182.
- Strle K, Drouin EE, Shen S, et al. Borrelia burgdorferi stimulates macrophages to secrete higher levels of cytokines and chemokines than Borrelia afzelii or Borrelia garinii. J Infect Dis 2009; 200:1936.
- Kurtenbach K, De Michelis S, Etti S, et al. Host association of Borrelia burgdorferi sensu lato--the key role of host complement. Trends Microbiol 2002; 10:74.
- Korenberg EI. Comparative ecology and epidemiology of lyme disease and tick-borne encephalitis in the former Soviet Union. Parasitol Today 1994; 10:157.
- Barbour AG, Bunikis J, Travinsky B, et al. Niche partitioning of Borrelia burgdorferi and Borrelia miyamotoi in the same tick vector and mammalian reservoir species. Am J Trop Med Hyg 2009; 81:1120.
- Barbour AG, Travinsky B. Evolution and distribution of the ospC Gene, a transferable serotype determinant of Borrelia burgdorferi. MBio 2010; 1.
- Lane RS, Quistad GB. Borreliacidal factor in the blood of the western fence lizard (Sceloporus occidentalis). J Parasitol 1998; 84:29.
- Wormser GP, Brisson D, Liveris D, et al. Borrelia burgdorferi genotype predicts the capacity for hematogenous dissemination during early Lyme disease. J Infect Dis 2008; 198:1358.
- Jones KL, Glickstein LJ, Damle N, et al. Borrelia burgdorferi genetic markers and disseminated disease in patients with early Lyme disease. J Clin Microbiol 2006; 44:4407.
- Seinost G, Dykhuizen DE, Dattwyler RJ, et al. Four clones of Borrelia burgdorferi sensu stricto cause invasive infection in humans. Infect Immun 1999; 67:3518.
- Liveris D, Varde S, Iyer R, et al. Genetic diversity of Borrelia burgdorferi in lyme disease patients as determined by culture versus direct PCR with clinical specimens. J Clin Microbiol 1999; 37:565.
- Wang G, Ojaimi C, Wu H, et al. Disease severity in a murine model of lyme borreliosis is associated with the genotype of the infecting Borrelia burgdorferi sensu stricto strain. J Infect Dis 2002; 186:782.
- Hanincová K, Ogden NH, Diuk-Wasser M, et al. Fitness variation of Borrelia burgdorferi sensu stricto strains in mice. Appl Environ Microbiol 2008; 74:153.