This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Embers, M. E.
Right arrow Articles by Philipp, M. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Embers, M. E.
Right arrow Articles by Philipp, M. T.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, January 2007, p. 90-93, Vol. 14, No. 1
1071-412X/07/$08.00+0     doi:10.1128/CVI.00266-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Borrelia burgdorferi Spirochetes That Harbor Only a Portion of the lp28-1 Plasmid Elicit Antibody Responses Detectable with the C6 Test for Lyme Disease{triangledown}

Monica E. Embers,1 Gary P. Wormser,2 Ira Schwartz,3 Dale S. Martin,1 and Mario T. Philipp1*

Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, Louisiana,1 Division of Infectious Diseases, Department of Medicine,2 Department of Microbiology & Immunology, New York Medical College, Valhalla, New York3

Received 21 July 2006/ Returned for modification 5 September 2006/ Accepted 6 November 2006


arrow
ABSTRACT
 
Detection of antibody to C6, a peptide that reproduces the sequence of the sixth invariable region within the central domain of the VlsE protein of Borrelia burgdorferi, is used currently for the serologic diagnosis of Lyme disease in humans. B. burgdorferi isolates taken from infected humans can be categorized into specific genetic subtypes (designated RST1, -2, and -3) by restriction fragment length polymorphisms in the 16S to 23S rRNA spacer sequence. Many of these, usually categorized as RST2, retain only segments of the linear plasmid lp28-1, which encodes VlsE. The VlsE genetic region is retained, but altered expression of this molecule could affect diagnosis by the C6 enzyme-linked immunosorbent assay (ELISA). Serum samples from patients infected with each of the three genotypes and from mice infected with three RST2 isolates were tested with the C6 ELISA. Such isolates elicited marked C6 responses in infected mice. The sensitivity of C6 antibody detection in patients infected with RST2 spirochetes was statistically indistinguishable from detection of RST1 and RST3 infections. These findings demonstrate that diagnosis by C6 ELISA remains effective for infection with all B. burgdorferi genotypes, including those with incomplete lp28-1 plasmids.


arrow
TEXT
 
The clinical progression of Lyme disease, a tick-borne illness that is caused by the spirochete Borrelia burgdorferi, is divided into early localized, early disseminated, and late stages. During the early localized phase, the disease usually manifests by a characteristic skin lesion, erythema migrans (EM). Several days or weeks later, the spirochetes may spread hematogenously and patients may develop early disseminated disease with dermatologic, cardiac, neurologic, and/or rheumatologic involvement. During the early disseminated phase, some patients exhibit dermatologic signs that appear as multiple EM (24, 27, 29, 33). Late disease presents mainly with arthritis or neurologic manifestations (28).

Evidence has been put forward to suggest that a major determinant of the risk of B. burgdorferi dissemination in Lyme disease patients with EM is the genotype of the infecting spirochetal strain. Three genotypes have been identified on the basis of restriction fragment length polymorphisms in the rRNA spacer region and have been designated RST1, -2, and -3 (16). Patients infected with RST1 spirochetes had the highest proportion of blood culture positivity (43%), those infected with RST2 spirochetes were intermediate (20%), and those with RST3 had the lowest proportion (3%). In general, persons with an RST1 infection had more symptoms and symptoms of greater severity than those with either RST2 or RST3 infection (32). Mice that were inoculated with RST1 organisms were significantly more likely to yield cultivable spirochetes from different organs and showed a significantly higher prevalence of both carditis and arthritis than did animals inoculated with RST3 spirochetes (30); RST2 isolates were not assessed. When the plasmid contents of the different human infectious types were assessed, RST2 spirochetes emerged as almost uniformly lacking lp56, lp38, and fragments of lp28-1 (six of seven isolates assessed) (4). In contrast, spirochetes of RST1 either had no missing plasmids (six of eight isolates) or lacked a circular plasmid of the cp32 family (two of eight isolates). Spirochetes of RST3 were more heterogeneous, lacking assorted plasmids, but no more than two each. Only one of six isolates had a segment of lp28-1 missing (4).

VlsE is an antigenic variation protein encoded by lp28-1. This molecule undergoes variation by gene conversion within interspersed variable regions of a central cassette (34). VlsE could be abnormally expressed or not expressed at all by RST2 spirochetes given that many isolates harbor an incomplete lp28-1 plasmid. Detection of antibody to C6, a peptide that reproduces the sequence of the sixth invariable region within the central domain of the VlsE protein of B. burgdorferi, is used currently for the serologic diagnosis of Lyme disease in humans (1, 5, 9, 12, 17, 18, 20-24) and in canines (3, 7, 8, 11, 14). As the C6 test emerges as a possible substitute for the two-tiered serologic algorithm (1), the absence of portions of lp28-1 in RST2 isolates could represent a problem. Prior to the studies presented here, the possibility remained that the sensitivity of C6 serology for infections with this spirochetal type could be diminished.

To ascertain whether the C6 peptide was expressed in a serologically detectable manner by RST2 spirochetes, we inoculated mice with three different RST2 isolates and serially assessed their C6 antibody responses in relation to that of an RST1 isolate. In addition, the serologic sensitivity of the C6 enzyme-linked immunosorbent assay (ELISA) was assessed in two groups of Lyme disease patients with EM infected with RST1 (or RST3) and RST2 spirochetes, respectively. Two B. burgdorferi RST2 clinical isolates, B265 and B376 (4), and the strain 297 (also RST2 [32]) were cultured in Barbour-Stoenner-Kelly-H (BSK-H) medium (Sigma, St. Louis, MO) and grown at 34°C to late log phase. Three C3H/HeN mice per isolate were infected with 104 cultured organisms via subcutaneous needle inoculation. Ear punch biopsy specimens were collected at 1 week postinfection and cultured in BSK-H. At 2, 14, and 21 days postinfection, blood was collected from each animal, with euthanasia and exsanguinations at day 21. The heart, bladder, spleen, axillary lymph nodes, tibiotarsal joints, and skin from the ears were collected, and ~1- to 2-mm2 pieces of each tissue were placed in BSK-H medium for culture at 34°C. Cultures were examined 7 to 10 days later for the presence of spirochetes.

The antibody responses of infected mice to the C6 region of VlsE were determined by peptide ELISA essentially as described previously (10). Mouse serum from each time point was assayed in triplicate at a dilution of 1:200. Goat anti-mouse immunoglobulin G (IgG) plus IgA plus IgM (heavy plus light chains) conjugated to horseradish peroxidase (Zymed Laboratories, San Francisco, CA) was used as the secondary antibody. Progression of the anti-C6 response, beginning at day 2 postinfection, was measured for each mouse individually. As controls, preimmune and day 21 sera from a mouse infected with B31.5A19 (an RST1 clonal isolate possessing all plasmids) were included.

Culture of ear biopsy specimens at 1 week postinfection and organ tissues at 21 days postinfection revealed dissemination of RST2 isolates within infected mice (data not shown). Spirochetes were cultured from the 7-day-postinfection ear biopsy specimens of all mice (three of three and three of three, respectively) infected with B265 and B376 but no mice (zero of three) infected with 297. At 21 days, the ear skin, heart, lymph nodes, and tibiotarsal joints of all mice (nine of nine) bore spirochetes. Several splenic (five of nine) cultures and one bladder culture did not contain spirochetes.

Mouse serum antibodies from days 2, 14, and 21 postinfection were tested by the C6 ELISA. As shown in Fig. 1, all mice generated an anti-C6 response that was weaker at day 14 but markedly elevated by day 21. Some variation existed between individual mice, but no difference in the responses generated by individual RST2 isolates was evident. The C6 antibody level of the B31.5A19-infected mouse was higher, but this may simply reflect the ability of RST1 spirochetes to rapidly proliferate and disseminate in mice (30).


Figure 1
View larger version (21K):
[in this window]
[in a new window]

  		FIG. 1. Serum antibody reactivity to the C6 peptide by mice infected with RST2 B. burgdorferi spirochetes. Optical density at 450 nm (O.D.450) for the combined value of triplicate samples is shown. Serum optical density values for each mouse and each time point are plotted individually, where the strain and mouse are shown in the x axis, e.g., B265-1 indicates strain B265 and mouse 1. The center bars in each set include the combined average values from three mice at the day 21 time point.

The patient population consisted of 79 patients who presented to the Lyme Disease Practice of the Westchester Medical Center between June 1991 and July 2000 with either a single EM (early localized disease, n = 61) or multiple EM (early disseminated disease, n = 18). This is a subgroup of a patient population (n = 120) that was C6 tested in a previous study (24). RST typing was available for 79 of these 120 patients; the former were thus included in the present study solely on this basis. A skin biopsy specimen or blood specimen from each patient was shown to contain cultivable B. burgdorferi spirochetes. The genotype of each cultured isolate was determined by PCR amplification of a portion of the 16S to 23S rRNA spacer followed by restriction fragment length polymorphism analysis as previously described (15, 16).

For human samples, C6 antibody titers were determined exactly as described previously (24). The serum from each of these patients was tested for reactivity to the C6 peptide by ELISA. All of the combined results are presented in Table 1. Of 79 patients, 69 tested positive for C6 antibodies on acute- or convalescent-phase serum samples, yielding an overall response in 87% of patients. This fraction is essentially the same as that obtained in the above-mentioned study that included the 120 patients from which 79 were RST typed (88%) (24). Thus, the selection of these 79 patients on the basis of availability of their RST typing did not bias the outcome with regard to overall sensitivity of C6 antibody detection. Among these patients, 88% of RST1-infected individuals, 89% of RST2-infected patients, and 85% of RST3-infected persons were positive for C6 antibodies (Table 1). The combined proportion of patients infected with types 1 and 3 (86.3%) that were C6 positive was lower than the proportion of RST2-infected patients that were C6 positive (88.5%, or approximately 89%). However, this difference was not statistically significant: a Z test for statistical analysis yielded, for Z of 0.2925, a two-tailed P value of 0.7707 and a one-tailed P value of 0.3962.


View this table:
[in this window]
[in a new window]

  		TABLE 1. Results of C6 antibody tests on Lyme disease patients infected with different subtypes of B. burgdorferi

The lp28-1 plasmid has previously been shown to be required for persistent infection in mice (6). Thus, clinical isolates taken from Lyme disease patients probably must possess at least some part of lp28-1 to survive. The presence of VlsE in that portion of lp28-1 that is retained is evident from PCR and Southern blot analyses of isolates (4). In this report, the demonstration of C6 antibody responses by mice infected with isolates known to harbor incomplete lp28-1 plasmids proves not only that VlsE is present in these isolates but also that it is antigenic in a manner equivalent to that of VlsE expressed by B. burgdorferi spirochetes that have complete lp28-1 plasmids.

The diagnosis of Lyme borreliosis is complicated by the genetic and subsequent antigenic variability that exists among B. burgdorferi species. The presence of multiple strains in an area of Lyme disease endemicity could also complicate diagnosis (2, 13, 19, 25, 26, 31). An antigen that contains epitopes which remain conserved and expressed across the B. burgdorferi sensu lato population is of extraordinary importance to diagnostic sensitivity and accuracy. The sixth invariable region of VlsE, from which the C6 ELISA was developed, is an immunogenic segment with those properties. In this series of experiments, we sought to assess the ability of the C6 test to detect infection with organisms of different genotypes with variable plasmid contents. The results revealed that the C6 test remains a viable option for serological diagnosis of Lyme disease regardless of RST genotype.


arrow
ACKNOWLEDGMENTS
 
This work was partially supported by NIH grants AI49976, RR00164 (M.T.P.), and AR41511 (I.S.).


arrow
FOOTNOTES
 
* Corresponding author. Mailing address: Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, 18703 Three Rivers Road, Covington, LA 70433. Phone: (985) 871-6221. Fax: (985) 871-6390. E-mail: Philipp{at}tpc.tulane.edu. Back

{triangledown} Published ahead of print on 15 November 2006. Back


arrow
REFERENCES
 
    1
  1. Bacon, R. M., B. J. Biggerstaff, M. E. Schriefer, R. D. Gilmore, Jr., M. T. Philipp, A. C. Steere, G. P. Wormser, A. R. Marques, and B. J. Johnson. 2003. Serodiagnosis of Lyme disease by kinetic enzyme-linked immunosorbent assay using recombinant VlsE1 or peptide antigens of Borrelia burgdorferi compared with 2-tiered testing using whole-cell lysates. J. Infect. Dis. 187:1187-1199.[CrossRef][Medline]
    2. 2
  2. Bunikis, J., U. Garpmo, J. Tsao, J. Berglund, D. Fish, and A. G. Barbour. 2004. Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe. Microbiology 150:1741-1755.[Abstract/Free Full Text]
    3. 3
  3. Duncan, A. W., M. T. Correa, J. F. Levine, and E. B. Breitschwerdt. 2005. The dog as a sentinel for human infection: prevalence of Borrelia burgdorferi C6 antibodies in dogs from southeastern and mid-Atlantic states. Vector Borne Zoonot. Dis. 5:101-109.[CrossRef]
    4. 4
  4. Iyer, R., O. Kalu, J. Purser, S. Norris, B. Stevenson, and I. Schwartz. 2003. Linear and circular plasmid content in Borrelia burgdorferi clinical isolates. Infect. Immun. 71:3699-3706.[Abstract/Free Full Text]
    5. 5
  5. Jansson, C., S. A. Carlsson, H. Granlund, P. Wahlberg, and D. Nyman. 2005. Analysis of Borrelia burgdorferi IgG antibodies with a combination of IgG ELISA and VlsE C6 peptide ELISA. Clin. Microbiol. Infect. 11:147-150.[CrossRef][Medline]
    6. 6
  6. Labandeira-Rey, M., J. Seshu, and J. T. Skare. 2003. The absence of linear plasmid 25 or 28-1 of Borrelia burgdorferi dramatically alters the kinetics of experimental infection via distinct mechanisms. Infect. Immun. 71:4608-4613.[Abstract/Free Full Text]
    7. 7
  7. Levy, S., T. P. O'Connor, J. L. Hanscom, and P. Shields. 2002. Utility of an in-office C6 ELISA test kit for determination of infection status of dogs naturally exposed to Borrelia burgdorferi. Vet. Ther. 3:308-315.[Medline]
    8. 8
  8. Levy, S. A. 2002. Use of a C6 ELISA test to evaluate the efficacy of a whole-cell bacterin for the prevention of naturally transmitted canine Borrelia burgdorferi infection. Vet. Ther. 3:420-424.[Medline]
    9. 9
  9. Liang, F. T., E. Aberer, M. Cinco, L. Gern, C. M. Hu, Y. N. Lobet, M. Ruscio, P. E. Voet, Jr., V. E. Weynants, and M. T. Philipp. 2000. Antigenic conservation of an immunodominant invariable region of the VlsE lipoprotein among European pathogenic genospecies of Borrelia burgdorferi SL. J. Infect. Dis. 182:1455-1462.[CrossRef][Medline]
    10. 10
  10. Liang, F. T., L. C. Bowers, and M. T. Philipp. 2001. C-terminal invariable domain of VlsE is immunodominant but its antigenicity is scarcely conserved among strains of Lyme disease spirochetes. Infect. Immun. 69:3224-3231. (Erratum, 69:5216.)[Abstract/Free Full Text]
    11. 11
  11. Liang, F. T., R. H. Jacobson, R. K. Straubinger, A. Grooters, and M. T. Philipp. 2000. Characterization of a Borrelia burgdorferi VlsE invariable region useful in canine Lyme disease serodiagnosis by enzyme-linked immunosorbent assay. J. Clin. Microbiol. 38:4160-4166.[Abstract/Free Full Text]
    12. 12
  12. Liang, F. T., A. C. Steere, A. R. Marques, B. J. Johnson, J. N. Miller, and M. T. Philipp. 1999. 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. 37:3990-3996.[Abstract/Free Full Text]
    13. 13
  13. Lin, T., J. H. Oliver, Jr., and L. Gao. 2003. Comparative analysis of Borrelia isolates from southeastern USA based on randomly amplified polymorphic DNA fingerprint and 16S ribosomal gene sequence analyses. FEMS Microbiol. Lett. 228:249-257.[CrossRef][Medline]
    14. 14
  14. Littman, M. P. 2003. Canine borreliosis. Vet. Clin. N. Am. Small Anim. Pract. 33:827-862.[CrossRef][Medline]
    15. 15
  15. Liveris, D., S. Varde, R. Iyer, S. Koenig, S. Bittker, D. Cooper, D. McKenna, J. Nowakowski, R. B. Nadelman, G. P. Wormser, and I. Schwartz. 1999. Genetic diversity of Borrelia burgdorferi in Lyme disease patients as determined by culture versus direct PCR with clinical specimens. J. Clin. Microbiol. 37:565-569.[Abstract/Free Full Text]
    16. 16
  16. Liveris, D., G. P. Wormser, J. Nowakowski, R. Nadelman, S. Bittker, D. Cooper, S. Varde, F. H. Moy, G. Forseter, C. S. Pavia, and I. Schwartz. 1996. Molecular typing of Borrelia burgdorferi from Lyme disease patients by PCR-restriction fragment length polymorphism analysis. J. Clin. Microbiol. 34:1306-1309.[Abstract]
    17. 17
  17. Marangoni, A., M. Sparacino, F. Cavrini, E. Storni, V. Mondardini, V. Sambri, and R. Cevenini. 2005. Comparative evaluation of three different ELISA methods for the diagnosis of early culture-confirmed Lyme disease in Italy. J. Med. Microbiol. 54:361-367.[Abstract/Free Full Text]
    18. 18
  18. Marangoni, A., M. Sparacino, V. Mondardini, F. Cavrini, E. Storni, M. Donati, R. Cevenini, and V. Sambri. 2005. Comparative evaluation of two enzyme linked immunosorbent assay methods and three Western blot methods for the diagnosis of culture-confirmed early Lyme borreliosis in Italy. New Microbiol. 28:37-43.[Medline]
    19. 19
  19. Mediannikov, O. Y., L. Ivanov, N. Zdanovskaya, R. Vorobyova, Y. Sidelnikov, P. E. Fournier, I. Tarasevich, and D. Raoult. 2005. Diversity of Borrelia burgdorferi sensu lato in Russian Far East. Microbiol. Immunol. 49:191-197.[Medline]
    20. 20
  20. Mogilyansky, E., C. C. Loa, M. E. Adelson, E. Mordechai, and R. C. Tilton. 2004. Comparison of Western immunoblotting and the C6 Lyme antibody test for laboratory detection of Lyme disease. Clin. Diagn. Lab. Immunol. 11:924-929.[CrossRef][Medline]
    21. 21
  21. Nyman, D., L. Willen, C. Jansson, S. A. Carlsson, H. Granlund, and P. Wahlberg. 2006. VlsE C6 peptide and IgG ELISA antibody analysis for clinical diagnosis of Lyme borreliosis in an endemic area. Clin. Microbiol. Infect. 12:496-497.[CrossRef][Medline]
    22. 22
  22. Panelius, J., P. Lahdenne, H. Saxen, S. A. Carlsson, T. Heikkila, M. Peltomaa, A. Lauhio, and I. Seppala. 2003. Diagnosis of Lyme neuroborreliosis with antibodies to recombinant proteins DbpA, BBK32, and OspC, and VlsE IR6 peptide. J. Neurol. 250:1318-1327.[CrossRef][Medline]
    23. 23
  23. Peltomaa, M., G. McHugh, and A. C. Steere. 2004. The VlsE (IR6) peptide ELISA in the serodiagnosis of lyme facial paralysis. Otol. Neurotol. 25:838-841.[CrossRef][Medline]
    24. 24
  24. Philipp, M. T., G. P. Wormser, A. R. Marques, S. Bittker, D. S. Martin, J. Nowakowski, and L. G. Dally. 2005. A decline in C6 antibody titer occurs in successfully treated patients with culture-confirmed early localized or early disseminated Lyme borreliosis. Clin. Diagn. Lab. Immunol. 12:1069-1074.[CrossRef][Medline]
    25. 25
  25. Qiu, W.-G., S. E. Schutzer, J. F. Bruno, O. Attie, Y. Xu, J. J. Dunn, C. M. Fraser, S. R. Casjens, and B. J. Luft. 2004. Genetic exchange and plasmid transfers in Borrelia burgdorferi sensu stricto revealed by three-way genome comparisons and multilocus sequence typing. Proc. Natl. Acad. Sci. USA 101:14150-14155.[Abstract/Free Full Text]
    26. 26
  26. Ruzic-Sabljic, E., F. Strle, J. Cimperman, V. Maraspin, S. Lotric-Furlan, and D. Pleterski-Rigler. 2000. Characterisation of Borrelia burgdorferi sensu lato strains isolated from patients with skin manifestations of Lyme borreliosis residing in Slovenia. J. Med. Microbiol. 49:47-53.[Abstract/Free Full Text]
    27. 27
  27. Smith, R. P., R. T. Schoen, D. W. Rahn, V. K. Sikand, J. Nowakowski, D. L. Parenti, M. S. Holman, D. H. Persing, and A. C. Steere. 2002. Clinical characteristics and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans. Ann. Intern. Med. 136:421-428.[Abstract/Free Full Text]
    28. 28
  28. Steere, A. C. 2001. Lyme disease. N. Engl. J. Med. 345:115-125.[Free Full Text]
    29. 29
  29. Strle, F., R. B. Nadelman, J. Cimperman, J. Nowakowski, R. N. Picken, I. Schwartz, V. Maraspin, M. E. Aguero-Rosenfeld, S. Varde, S. Lotric-Furlan, and G. P. Wormser. 1999. Comparison of culture-confirmed erythema migrans caused by Borrelia burgdorferi sensu stricto in New York State and by Borrelia afzelii in Slovenia. Ann. Intern. Med. 130:32-36.[Abstract/Free Full Text]
    30. 30
  30. Wang, G., C. Ojaimi, R. Iyer, V. Saksenberg, S. A. McClain, G. P. Wormser, and I. Schwartz. 2001. Impact of genotypic variation of Borrelia burgdorferi sensu stricto on kinetics of dissemination and severity of disease in C3H/HeJ mice. Infect. Immun. 69:4303-4312.[Abstract/Free Full Text]
    31. 31
  31. Wilske, B. 2003. Diagnosis of Lyme borreliosis in Europe. Vector Borne Zoonot. Dis. 3:215-227.[CrossRef]
    32. 32
  32. Wormser, G. P., D. Liveris, J. Nowakowski, R. B. Nadelman, L. F. Cavaliere, D. McKenna, D. Holmgren, and I. Schwartz. 1999. Association of specific subtypes of Borrelia burgdorferi with hematogenous dissemination in early Lyme disease. J. Infect. Dis. 180:720-725.[CrossRef][Medline]
    33. 33
  33. Wormser, G. P., E. Masters, J. Nowakowski, D. McKenna, D. Holmgren, K. Ma, L. Ihde, L. F. Cavaliere, and R. B. Nadelman. 2005. Prospective clinical evaluation of patients from Missouri and New York with erythema migrans-like skin lesions. Clin. Infect. Dis. 41:958-965.[CrossRef][Medline]
    34. 34
  34. Zhang, J. R., J. M. Hardham, A. G. Barbour, and S. J. Norris. 1997. Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes. Cell 89:275-285. (Erratum, 95:447, 1999.)[CrossRef][Medline]

Clinical and Vaccine Immunology, January 2007, p. 90-93, Vol. 14, No. 1
1071-412X/07/$08.00+0     doi:10.1128/CVI.00266-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Coleman, A. S., Pal, U. (2009). BBK07, a Dominant In Vivo Antigen of Borrelia burgdorferi, Is a Potential Marker for Serodiagnosis of Lyme Disease. CVI 16: 1569-1575 [Abstract] [Full Text]  
  • Ledue, T. B., Collins, M. F., Young, J., Schriefer, M. E. (2008). Evaluation of the Recombinant VlsE-Based Liaison Chemiluminescence Immunoassay for Detection of Borrelia burgdorferi and Diagnosis of Lyme Disease. CVI 15: 1796-1804 [Abstract] [Full Text]  

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Embers, M. E.
Right arrow Articles by Philipp, M. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Embers, M. E.
Right arrow Articles by Philipp, M. T.

Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»