Genetic Diversity of ospC in a Local Population of Borrelia burgdorferi sensu stricto

Corresponding author: Daniel E. Dykhuizen, Department of Ecology and Evolution, State University of New York, Stony Brook, NY 11794-5245., dandyk{at}life.bio.sunysb.edu (E-mail)

Communicating editor: W. F. EANES

The outer surface protein, OspC, is highly variable in Borrelia burgdorferi sensu stricto, the agent of Lyme disease. We have shown that even within a single population OspC is highly variable. The variation of ospA and ospC in the 40 infected deer ticks collected from a single site on Shelter Island, New York, was determined using PCR-SSCP. There is very strong apparent linkage disequilibrium between ospA and ospC alleles, even though they are located on separate plasmids. Thirteen discernible SSCP mobility classes for ospC were identified and the DNA sequence for each was determined. These sequences, combined with 40 GenBank sequences, allow us to define 19 major ospC groups. Sequences within a major ospC group are, on average, <1% different from each other, while sequences between major ospC groups are, on average, ~20% different. The tick sample contains 11 major ospC groups, GenBank contains 16 groups, with 8 groups found in both samples. Thus, the ospC variation within a local population is almost as great as the variation of a similar-sized sample of the entire species. The Ewens-Watterson-Slatkin test of allele frequency showed significant deviation from the neutral expectation, indicating balancing selection for these major ospC groups. The variation represented by major ospC groups needs to be considered if the OspC protein is to be used as a serodiagnostic antigen or a vaccine.

This article has been cited by other articles:

				MLST of housekeeping genes captures geographic population structure and suggests a European origin of Borrelia burgdorferi PNAS, June 24, 2008; 105(25): 8730 - 8735.

				D. E. Dykhuizen, D. Brisson, S. Sandigursky, G. P. Wormser, J. Nowakowski, R. B. Nadelman, and I. Schwartz The Propensity of Different Borrelia burgdorferi sensu stricto Genotypes to Cause Disseminated Infections in Humans Am J Trop Med Hyg, May 1, 2008; 78(5): 806 - 810. [Abstract] [Full Text] [PDF]

				P. Kraiczy, A. Seling, C. A. Brissette, E. Rossmann, K.-P. Hunfeld, T. Bykowski, L. H. Burns, M. J. Troese, A. E. Cooley, J. C. Miller, et al. Borrelia burgdorferi Complement Regulator-Acquiring Surface Protein 2 (CspZ) as a Serological Marker of Human Lyme Disease Clin. Vaccine Immunol., March 1, 2008; 15(3): 484 - 491. [Abstract] [Full Text] [PDF]

				K. Hanincova, N. H. Ogden, M. Diuk-Wasser, C. J. Pappas, R. Iyer, D. Fish, I. Schwartz, and K. Kurtenbach Fitness Variation of Borrelia burgdorferi Sensu Stricto Strains in Mice Appl. Envir. Microbiol., January 1, 2008; 74(1): 153 - 157. [Abstract] [Full Text] [PDF]

				C. G. Earnhart and R. T. Marconi OspC Phylogenetic Analyses Support the Feasibility of a Broadly Protective Polyvalent Chimeric Lyme Disease Vaccine Clin. Vaccine Immunol., May 1, 2007; 14(5): 628 - 634. [Abstract] [Full Text] [PDF]

				K. L. Jones, L. J. Glickstein, N. Damle, V. K. Sikand, G. McHugh, and A. C. Steere Borrelia burgdorferi Genetic Markers and Disseminated Disease in Patients with Early Lyme Disease J. Clin. Microbiol., December 1, 2006; 44(12): 4407 - 4413. [Abstract] [Full Text] [PDF]

				E. L. Buckles, C. G. Earnhart, and R. T. Marconi Analysis of Antibody Response in Humans to the Type A OspC Loop 5 Domain and Assessment of the Potential Utility of the Loop 5 Epitope in Lyme Disease Vaccine Development Clin. Vaccine Immunol., October 1, 2006; 13(10): 1162 - 1165. [Abstract] [Full Text] [PDF]

				C.-M. Kim, Y.-H. Yi, D.-H. Yu, M.-J. Lee, M.-R. Cho, A. R. Desai, S. Shringi, T. A. Klein, H.-C. Kim, J.-W. Song, et al. Tick-Borne Rickettsial Pathogens in Ticks and Small Mammals in Korea Appl. Envir. Microbiol., September 1, 2006; 72(9): 5766 - 5776. [Abstract] [Full Text] [PDF]

				C. L. Lawson, B. H. Yung, A. G. Barbour, and W. R. Zuckert Crystal Structure of Neurotropism-Associated Variable Surface Protein 1 (Vsp1) of Borrelia turicatae. J. Bacteriol., June 1, 2006; 188(12): 4522 - 4530. [Abstract] [Full Text] [PDF]

				D. BRISSON and D. E. DYKHUIZEN A MODEST MODEL EXPLAINS THE DISTRIBUTION AND ABUNDANCE OF BORRELIA BURGDORFERI STRAINS Am J Trop Med Hyg, April 1, 2006; 74(4): 615 - 622. [Abstract] [Full Text] [PDF]

				C. G. Earnhart, E. L. Buckles, J. S. Dumler, and R. T. Marconi Demonstration of OspC Type Diversity in Invasive Human Lyme Disease Isolates and Identification of Previously Uncharacterized Epitopes That Define the Specificity of the OspC Murine Antibody Response Infect. Immun., December 1, 2005; 73(12): 7869 - 7877. [Abstract] [Full Text] [PDF]

				S. F. Porcella, S. J. Raffel, D. E. Anderson Jr., S. D. Gilk, J. L. Bono, M. E. Schrumpf, and T. G. Schwan Variable Tick Protein in Two Genomic Groups of the Relapsing Fever Spirochete Borrelia hermsii in Western North America Infect. Immun., October 1, 2005; 73(10): 6647 - 6658. [Abstract] [Full Text] [PDF]

				S. D. Lovrich, D. A. Jobe, R. F. Schell, and S. M. Callister Borreliacidal OspC Antibodies Specific for a Highly Conserved Epitope Are Immunodominant in Human Lyme Disease and Do Not Occur in Mice or Hamsters Clin. Vaccine Immunol., June 1, 2005; 12(6): 746 - 751. [Abstract] [Full Text] [PDF]

				M. Y. Alghaferi, J. M. Anderson, J. Park, P. G. Auwaerter, J. N. Aucott, D. E. Norris, and J. S. Dumler Borrelia burgdorferi ospC Heterogeneity among Human and Murine Isolates from a Defined Region of Northern Maryland and Southern Pennsylvania: Lack of Correlation with Invasive and Noninvasive Genotypes J. Clin. Microbiol., April 1, 2005; 43(4): 1879 - 1884. [Abstract] [Full Text] [PDF]

				M. Derdakova, V. Dudioak, B. Brei, J. S. Brownstein, I. Schwartz, and D. Fish Interaction and Transmission of Two Borrelia burgdorferi Sensu Stricto Strains in a Tick-Rodent Maintenance System Appl. Envir. Microbiol., November 1, 2004; 70(11): 6783 - 6788. [Abstract] [Full Text] [PDF]

				D. Brisson and D. E. Dykhuizen ospC Diversity in Borrelia burgdorferi: Different Hosts Are Different Niches Genetics, October 1, 2004; 168(2): 713 - 722. [Abstract] [Full Text] [PDF]

				W.-G. Qiu, S. E. Schutzer, J. F. Bruno, O. Attie, Y. Xu, J. J. Dunn, C. M. Fraser, S. R. Casjens, and B. J. Luft Genetic exchange and plasmid transfers in Borrelia burgdorferi sensu stricto revealed by three-way genome comparisons and multilocus sequence typing PNAS, September 28, 2004; 101(39): 14150 - 14155. [Abstract] [Full Text] [PDF]

				J. Bunikis, U. Garpmo, J. Tsao, J. Berglund, D. Fish, and A. G. Barbour Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe Microbiology, June 1, 2004; 150(6): 1741 - 1755. [Abstract] [Full Text] [PDF]

				D. Liveris, V. Mulay, and I. Schwartz Functional Properties of Borrelia burgdorferi recA J. Bacteriol., April 15, 2004; 186(8): 2275 - 2280. [Abstract] [Full Text] [PDF]

				V. Lagal, D. Postic, E. Ruzic-Sabljic, and G. Baranton Genetic Diversity among Borrelia Strains Determined by Single-Strand Conformation Polymorphism Analysis of the ospC Gene and Its Association with Invasiveness J. Clin. Microbiol., November 1, 2003; 41(11): 5059 - 5065. [Abstract] [Full Text] [PDF]

				W.-L. Wu, B. A. Schaal, C.-Y. Hwang, M.-D. Hwang, Y.-C. Chiang, and T.-Y. Chiang Characterization and adaptive evolution of {alpha}-tubulin genes in the Miscanthus sinensis complex (Poaceae) Am. J. Botany, October 1, 2003; 90(10): 1513 - 1521. [Abstract] [Full Text] [PDF]

				D. A. Jobe, S. D. Lovrich, R. F. Schell, and S. M. Callister C-Terminal Region of Outer Surface Protein C Binds Borreliacidal Antibodies in Sera from Patients with Lyme Disease Clin. Vaccine Immunol., July 1, 2003; 10(4): 573 - 578. [Abstract] [Full Text] [PDF]

				R. Iyer, O. Kalu, J. Purser, S. Norris, B. Stevenson, and I. Schwartz Linear and Circular Plasmid Content in Borrelia burgdorferi Clinical Isolates Infect. Immun., July 1, 2003; 71(7): 3699 - 3706. [Abstract] [Full Text] [PDF]

				A. R. Pachner, D. Dail, L. Li, L. Gurey, S. Feng, E. Hodzic, and S. Barthold Humoral Immune Response Associated with Lyme Borreliosis in Nonhuman Primates: Analysis by Immunoblotting and Enzyme-Linked Immunosorbent Assay with Sonicates or Recombinant Proteins Clin. Vaccine Immunol., November 1, 2002; 9(6): 1348 - 1355. [Abstract] [Full Text] [PDF]

				T. Lin, J. H. Oliver Jr., and L. Gao Genetic Diversity of the Outer Surface Protein C Gene of Southern Borrelia Isolates and Its Possible Epidemiological, Clinical, and Pathogenetic Implications J. Clin. Microbiol., July 1, 2002; 40(7): 2572 - 2583. [Abstract] [Full Text] [PDF]

				W.-G. Qiu, D. E. Dykhuizen, M. S. Acosta, and B. J. Luft Geographic Uniformity of the Lyme Disease Spirochete (Borrelia burgdorferi) and Its Shared History With Tick Vector (Ixodes scapularis) in the Northeastern United States Genetics, March 1, 2002; 160(3): 833 - 849. [Abstract] [Full Text] [PDF]

				F. T. Liang, M. B. Jacobs, L. C. Bowers, and M. T. Philipp An Immune Evasion Mechanism for Spirochetal Persistence in Lyme Borreliosis J. Exp. Med., February 11, 2002; 195(4): 415 - 422. [Abstract] [Full Text] [PDF]

				R. Iyer, D. Liveris, A. Adams, J. Nowakowski, D. McKenna, S. Bittker, D. Cooper, G. P. Wormser, and I. Schwartz Characterization of Borrelia burgdorferi Isolated from Erythema Migrans Lesions: Interrelationship of Three Molecular Typing Methods J. Clin. Microbiol., August 1, 2001; 39(8): 2954 - 2957. [Abstract] [Full Text] [PDF]

				M. J. C. Gomes-Solecki, J. J. Dunn, B. J. Luft, J. Castillo, D. E. Dykhuizen, X. Yang, J. D. Glass, and R. J. Dattwyler Recombinant Chimeric Borrelia Proteins for Diagnosis of Lyme Disease J. Clin. Microbiol., July 1, 2000; 38(7): 2530 - 2535. [Abstract] [Full Text]

				B. Rannala, W.-G. Qiu, and D. E. Dykhuizen Methods for Estimating Gene Frequencies and Detecting Selection in Bacterial Populations Genetics, June 1, 2000; 155(2): 499 - 508. [Abstract] [Full Text]

				J. C. Miller, N. El-Hage, K. Babb, and B. Stevenson Borrelia burgdorferi B31 Erp Proteins That Are Dominant Immunoblot Antigens of Animals Infected with Isolate B31 Are Recognized by Only a Subset of Human Lyme Disease Patient Sera J. Clin. Microbiol., April 1, 2000; 38(4): 1569 - 1574. [Abstract] [Full Text]

				F. T. Liang, A. C. Steere, A. R. Marques, B. J. B. Johnson, J. N. Miller, and M. T. Philipp Sensitive and Specific Serodiagnosis of Lyme Disease by Enzyme-Linked Immunosorbent Assay with a Peptide Based on an Immunodominant Conserved Region of Borrelia burgdorferi VlsE J. Clin. Microbiol., December 1, 1999; 37(12): 3990 - 3996. [Abstract] [Full Text]

				E. K. Hofmeister, G. E. Glass, J. E. Childs, and D. H. Persing Population Dynamics of a Naturally Occurring Heterogeneous Mixture of Borrelia burgdorferi Clones Infect. Immun., November 1, 1999; 67(11): 5709 - 5716. [Abstract] [Full Text] [PDF]

				G. Seinost, W. T. Golde, B. W. Berger, J. J. Dunn, D. Qiu, D. S. Dunkin, D. E. Dykhuizen, B. J. Luft, and R. J. Dattwyler Infection With Multiple Strains of Borrelia burgdorferi Sensu Stricto in Patients With Lyme Disease Arch Dermatol, November 1, 1999; 135(11): 1329 - 1333. [Abstract] [Full Text] [PDF]

				W. R. Zuckert, T. A. Kerentseva, C. L. Lawson, and A. G. Barbour Structural Conservation of Neurotropism-associated VspA within the Variable Borrelia Vsp-OspC Lipoprotein Family J. Biol. Chem., January 5, 2001; 276(1): 457 - 463. [Abstract] [Full Text] [PDF]

				S. M. Rich, S. A. Sawyer, and A. G. Barbour Antigen polymorphism in Borrelia hermsii, a clonal pathogenic bacterium PNAS, December 18, 2001; 98(26): 15038 - 15043. [Abstract] [Full Text] [PDF]