Lyme Disease Annotated Bibliography

Annotated Bibliography

Alao, O.R., and Decker, C.F. (2012). Lyme Disease. Disease-a-Month 58, 335–345. Link Here

  • The authors of this paper provide a great synopsis of the many aspects and areas involving Lyme disease including epidemiology, diagnosis, and treatment options.

Bankhead, T., and Chaconas, G. (2007). The role of VlsE antigenic variation in the Lyme disease spirochete: persistence through a mechanism that differs from other pathogens. Molecular Microbiology 65, 1547–1558. doi: 10.1111/j.1365-2958.2007.05895.x

  • The authors of this paper investigate the role of vlsE antigenic variation in virulence and infection of mice. They found that upon removal of the vlsE locus, it is an absolute requirement for persistence in the mouse host.

Bhate, C., and Schwartz, R.A. (2011). Lyme disease: Part I. Advances and perspectives. Journal of the American Academy of Dermatology 64, 619–636. Link here

  • The authors present a great review of Lyme disease with a dermatological perspective. It explains the different stages of skin manifestations of Lyme disease, as well as provides a good historical account of the disease.

Bhattacharjee, A., Oeemig, J.S., Kolodziejczyk, R., Meri, T., Kajander, T., Lehtinen, M.J., Iwaï, H., Jokiranta, T.S., and Goldman, A. (2013). Structural basis for complement evasion by Lyme disease pathogen Borrelia burgdorferi. J. Biol. Chem. 288, 18685–18695. doi: 10.1074/jbc.M113.459040

  • Authors of this paper investigated the role of OspE in helping B. burgdorferi evade the immune system. They obtained a solution structure of OspE by NMR and the x-ray structure of the OspE and factor H C-terminal domain complex. They provide a molecular basis for evasion of innate immunity and suggests how OspE could be used as a potential vaccine antigen.

Branda, J.A., Linskey, K., Kim, Y.A., Steere, A.C., and Ferraro, M.J. (2011). Two-Tiered Antibody Testing for Lyme Disease With Use of 2 Enzyme Immunoassays, a Whole-Cell Sonicate Enzyme Immunoassay Followed by a VlsE C6 Peptide Enzyme Immunoassay. Clinical Infectious Diseases 53, 541–547. doi: 10.1093/cid/cir464

  • The authors attempt to improve methods of Lyme disease antibody testing by making slight modifications to the  2-tiered testing approach. They found that their methods matched the sensitivity of the 2-tiered test, without the drawbacks.

Burgdorfer, W., Barbour, A.G., Hayes, S.F., Benach, J.L., Grunwaldt, E., and Davis, J.P. (1982). Lyme disease-a tick-borne spirochetosis? Science 216, 1317–1319. doi: 10.1126/science.7043737

  • This is the first paper to have identified a treponema-like spirochete as the tick vector of Lyme disease. This spirochete was named after the author and is known as Borrelia burgdorferi.

Bykowski, T., Babb, K., Von Lackum, K., Riley, S.P., Norris, S.J., and Stevenson, B. (2006). Transcriptional Regulation of the Borrelia burgdorferi Antigenically Variable VlsE Surface Protein. Journal of Bacteriology 188, 27–27. doi: 10.1128/JB.00229-06

  • The authors of this paper report that B. burgdorferi controls vlsE transcription levels in response to environmental cues. The obtained data which suggested the involvement of DNA-binding proteins in the regulation of vlsE at the level of transcriptional initiation.

Casjens, S., Palmer, N., van Vugt, R., Huang, W.M., Stevenson, B., Rosa, P., Lathigra, R., Sutton, G., Peterson, J., Dodson, R.J., et al. (2000). 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. 35, 490–516. doi: 10.1046/j.1365-2958.2000.01698.x

  • The authors of this paper obtained the entire genomic sequence of B. burgdorferi, which contains 12 linear and circular plasmids. Through analysis of the genome, they have observed there may have been extensive DNA rearrangement among many of the linear plasmids. Over 90% of the genes on these plasmids have no similarity to genes outside Borrelia, suggesting they perform specialized functions.

Chandra, A., Latov, N., Wormser, G.P., Marques, A.R., and Alaedini, A. (2011). Epitope mapping of antibodies to VlsE protein of Borrelia burgdorferi in post-Lyme disease syndrome. Clinical Immunology 141, 103–110. doi: 10.1016/j.clim.2011.06.005

  • This study was aimed at characterizing the epitopes of VlsE targeted by the antibody response in patients with post-Lyme disease syndrome. Epitope mapping was carried out by use of microarrays and the crystal structure if VlsE was obtained.

CDC Lyme Disease Transmission. Here.

  • The CDC website information about Lyme disease transmission.

Eicken, C., Sharma, V., Klabunde, T., Lawrenz, M.B., Hardham, J.M., Norris, S.J., and Sacchettini, J.C. (2002). Crystal Structure of Lyme Disease Variable Surface Antigen VlsE of Borrelia burgdorferi. J. Biol. Chem. 277, 21691–21696. doi: 10.1074/jbc.M201547200

  • The authors of this paper were able to obtain a crystal structure of the VslE protein and determined the variable loop regions are protecting the invariable regions of the protein from antibodies.

Embers, M.E., Ramamoorthy, R., and Philipp, M.T. (2004). Survival strategies of Borrelia burgdorferi, the etiologic agent of Lyme disease. Microbes & Infection 6, 312. doi: 10.1016/j.micinf.2003.11.014

  • This is a great review article, which discusses the supporting evidence for possible ways in which B. burgdorferi evades the immune system and persists in the mammalian host.

Fraser, C.M., Casjens, S., Huang, W.M., Sutton, G.G., Clayton, R., Lathigra, R., White, O., Ketchum, K.A., Dodson, R., Hickey, E.K., et al. (1997). Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature 390, 580–586. Link Here

  • The authors of this paper successfully obtained the genomic sequence of B. burgdorferi.

Hefty, P.S., Jolliff, S.E., Caimano, M.J., Wikel, S.K., and Akins, D.R. (2002). Changes in temporal and spatial patterns of outer surface lipoprotein expression generate population heterogeneity and antigenic diversity in the Lyme disease spirochete, Borrelia burgdorferi. Infect. Immun. 70, 3468–3478. doi: 10.1128/IAI.70.7.3468-3478.2002

  • The authors examined the function of cell surface lipoproteins, OspE/F/Elp. They found that antigenically diverse spirochetes can be generated during infection by changes in both when and where these lipoproteins are expressed. They suggest that these regulatory mechanisms likely contribute to the overall parasitic strategy of B. burgdorferi in maintaining persisten infections.

Hellwage, J., Meri, T., Heikkilä, T., Alitalo, A., Panelius, J., Lahdenne, P., Seppälä, I.J., and Meri, S. (2000). The complement regulator factor H binds to the surface protein OspE of Borrelia burgdorferi. J. Biol. Chem. DOI: 10.1074/jbc.M007994200

  • This was the landmark paper that showed that OspE of Borrelia burgdorferi binds to factor H and may play a role in complement evasion.

Kawabata, H., Myouga, F., Inagaki, Y., Murai, N., and Watanabe, H. (1998b). Genetic and immunological analyses of Vls (VMP-like sequences) of Borrelia burgdorferi. Microb. Pathog. 24, 155–166. Available here.

  • This article investigates the promiscuous recombination within the vlsE cassette region. Silent vls cassettes recombine in the vlsE region, which replaces and degrades the previously expressed segments. This provides evidence for a gene conversion mechanism in VlsE antigenic variation.

Lerner, M.B., Dailey, J., Goldsmith, B.R., Brisson, D., and Johnson, A.T.C. (2013). Detecting Lyme disease using antibody-functionalized single-walled carbon nanotube transistors. Biosens Bioelectron 45, 163–167. doi: 10.1016/j.bios.2013.01.035

  • Here the authors examined the potential of antibody-functionalized single-walled carbon nanotube field-effect transistors to use as a fast and accurate sensor for a Lyme disease antigen. The sensor effectively detected antigen in buffer at concentration as low as 1ng/ml. The speed and sensitivity of the biosensor make it an ideal candidate for development as a medical diagnostic test.

Liang, F.T., Jacobs, M.B., Bowers, L.C., and Philipp, M.T. (2002). An immune evasion mechanism for spirochetal persistence in Lyme borreliosis. J. Exp. Med. 195, 415–422. Link here

  • This paper showed that OspC expression is downregulated and upregulated in response to OspC antibody in the environment.

Liang, F.T., Alvarez, A.L., Gu, Y., Nowling, J.M., Ramamoorthy, R., and Philipp, M.T. (1999). An immunodominant conserved region within the variable domain of VlsE, the variable surface antigen of Borrelia burgdorferi. J. Immunol. 163, 5566–5573. Link Here

  • This paper provided the landmark discovery that IR6 is a very conserved region found in the invariable region of VlsE

Loïc Coutte, Botkin, D.J., Gao, L., and Norris, S.J. (2009). Detailed Analysis of Sequence Changes Occurring during vlsE Antigenic Variation in the Mouse Model of Borrelia burgdorferi Infection. PLoS Pathogens 5, 1–14. doi: 10.1371/journal.ppat.1000293

  • Authors performed an in depth and very detailed analysis of the change in vlsE sequence over time of infection. They suggest that the increasd frequency and complexity of vlsE sequence changes observed in clones recovered from immunocompetent mice is due to rapid clearance of relatively invariant clones by variable region-specific anti-VlsE antibody responses.

Marques, A. R. (2010). Lyme Disease: A Review. Curr Allergy Asthma Rep. 10:13-20. doi: 10.1007/s11882-009-0077-3

  • Marques provides a terrific outline of the different laboratory methods used to diagnose Lyme disease in the clinical setting.

Nocton, J.J., Dressler, F., Rutledge, B.J., Rys, P.N., Persing, D.H., and Steere, A.C. (1994). Detection of Borrelia burgdorferi DNA by Polymerase Chain Reaction in Synovial Fluid from Patients with Lyme Arthritis. New England Journal of Medicine 330, 229–234. doi: 10.1056/NEJM199401273300401

  • The authors of this paper attempted to understand Lyme arthritis and why it persists despite antibiotic therapy. They were able to use PCR to detect tB. burgdorferi DNA in synovial fluid. They conclude that PCR may be able to show whether Lyme arthritis that persists after antibiotic treatment is due to persistence of the spirochete or not.

Norris, S.J. (2006). Antigenic variation with a twist – the Borrelia story. Molecular Microbiology 60, 1319–1322. doi: 10.1111/j.1365-2958.2006.05204.x

  • This MicroCommentary compares the vlp gene from Borelia hermsii to the vlsE gene of Lyme disease. The author concludes that the vlsE antigenic variation locus has evolved a completely different antigenic variation mechanism involving segmental recombination from a contiguous array of vls silent cassettes.

Poljak, A., Comstedt, P., Hanner, M., Schüler, W., Meinke, A., Wizel, B., and Lundberg, U. (2012). Identification and characterization of Borrelia antigens as potential vaccine candidates against Lyme borreliosis. Vaccine 30, 4398–4406. doi: 10.1016/j.vaccine.2011.10.073

  • The authors of this study analyzed 15 vaccine antigen candidates that were specific to Borrelia species. They observed that Borreli-resistant mice contained a type 2 T cell response. Thus antigens mounting a type 2 T cell response might be preferred vaccine candidates for evaluation in animal models of Lyme borreliosis.

Revel, A.T., Talaat, A.M., and Norgard, M.V. (2001). DNA microarray analysis of differential gene expression in Borrelia burgdorferi, the Lyme disease spirochete. PNAS 99, 1562–1567. Link Here

  • This paper showed that changes in temperature and pH in the midgut of the tick activated the bacteria to change expression of its surface proteins

Smith, R.P., Schoen, R.T., Rahn, D.W., Sikand, V.K., Nowakowski, J., Parenti, D.L., Holman, M.S., Persing, D.H., and Steere, A.C. (2002). Clinical characteristics and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans. Ann. Intern. Med. 136, 421–428. Link Here

  • This study examines the clinical presentation and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans.

Steere, A.C., Schoen, R.T., and Taylor, E. (1987). The clinical evolution of Lyme arthritis. Ann. Intern. Med. 107, 725–731. Link Here

  • The authors of this paper performed a study in an attempt to track the progression of Lyme disease in patients who did not receive any antibiotic treatment.

Steere, A.C., and Glickstein, L. (2004). Elucidation of Lyme arthritis. Nature Reviews Immunology 4, 143–152. doi: 10.1038/nri1267

  • Steere provides a great review, which details the multiple hypotheses of how Lyme arthritis occurs. These include retained spirochetal antigens, nfection-induced autoimmunity, and bystander activation.

Steere, A.C., Coburn, J., and Glickstein, L. (2004). The emergence of Lyme disease. J Clin Invest 113, 1093–1101. doi: 10.1172/JCI200421681

  • In this article, Steere provides an incredibly useful review of the history and emergence of Lyme disease. He provides a broad overview of the biology of B. burgdorferi, clinical manifestations and disease pathogenesis, as well as syndromes, diagnosis, treatment, and prevention of disease.

Yang, X.F., Pal, U., Alani, S.M., Fikrig, E., and Norgard, M.V. (2004). Essential Role for OspA/B in the Life Cycle of the Lyme Disease Spirochete. J Exp Med 199, 641–648. Link Here

  • This paper provides insight into the function of OspA/B, which was shown to be essential for B. burgdorferi colonization of and survival within tick midguts.

Zhang, J.R., and Norris, S.J. (1998). Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion. Infect. Immun. 66, 3698–3704. Link Here

  • This paper provided evidence for the gene conversion mechanism of the VlsE protein.

Zhang, J.R., Hardham, J.M., Barbour, A.G., and Norris, S.J. (1997). Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes. Cell 89, 275–285. Link Here

  • This paper shows the potential for the vlsE locus to form many different recombinant forms of VlsE.