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Published in: BMC Infectious Diseases 1/2002

Open Access 01-12-2002 | Research article

Characterisation of silent and active genes for a variable large protein of Borrelia recurrentis

Authors: Vincent Vidal, Sally Cutler, Ian G Scragg, David JM Wright, Dominic Kwiatkowski

Published in: BMC Infectious Diseases | Issue 1/2002

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Abstract

Background

We report the characterisation of the variable large protein (vlp) gene expressed by clinical isolate A1 of Borrelia recurrentis; the agent of the life-threatening disease louse-borne relapsing fever.

Methods

The major vlp protein of this isolate was characterised and a DNA probe created. Use of this together with standard molecular methods was used to determine the location of the vlp1 B. recurrentis A1 gene in both this and other isolates.

Results

This isolate was found to carry silent and expressed copies of the vlp1 B. recurrentis A1 gene on plasmids of 54 kbp and 24 kbp respectively, whereas a different isolate, A17, had only the silent vlp1 B. recurrentis A17 on a 54 kbp plasmid. Silent and expressed vlp1 have identical mature protein coding regions but have different 5' regions, both containing different potential lipoprotein leader sequences. Only one form of vlp1 is transcribed in the A1 isolate of B. recurrentis, yet both 5' upstream sequences of this vlp1 gene possess features of bacterial promoters.

Conclusion

Taken together these results suggest that antigenic variation in B. recurrentis may result from recombination of variable large and small protein genes at the junction between lipoprotein leader sequence and mature protein coding region. However, this hypothetical model needs to be validated by further identification of expressed and silent variant protein genes in other B. recurrentis isolates.
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Literature
1.
go back to reference Barbour AG, Tessier SL, Stoenner HG: Variable major proteins of Borrelia hermsii. J Exp Med. 1982, 156: 1312-1324.CrossRefPubMed Barbour AG, Tessier SL, Stoenner HG: Variable major proteins of Borrelia hermsii. J Exp Med. 1982, 156: 1312-1324.CrossRefPubMed
2.
go back to reference Stoenner HG, Dodd T, Larsen C: Antigenic variation of Borrelia hermsii. J Exp Med. 1982, 156: 1297-1311.CrossRefPubMed Stoenner HG, Dodd T, Larsen C: Antigenic variation of Borrelia hermsii. J Exp Med. 1982, 156: 1297-1311.CrossRefPubMed
3.
go back to reference Kitten T, Barbour AG: Juxtaposition of expressed variable antigen genes with a conserved telomere in the bacterium Borrelia hermsii. Proc Natl Acad Sci U S A. 1990, 87: 6077-6081.CrossRefPubMedPubMedCentral Kitten T, Barbour AG: Juxtaposition of expressed variable antigen genes with a conserved telomere in the bacterium Borrelia hermsii. Proc Natl Acad Sci U S A. 1990, 87: 6077-6081.CrossRefPubMedPubMedCentral
4.
go back to reference Plasterk RH, Simon MI, Barbour AG: Transposition of structural genes to an expression sequence on a linear plasmid causes antigenic variation in the bacterium Borrelia hermsii. Nature. 1985, 318: 257-263.CrossRefPubMed Plasterk RH, Simon MI, Barbour AG: Transposition of structural genes to an expression sequence on a linear plasmid causes antigenic variation in the bacterium Borrelia hermsii. Nature. 1985, 318: 257-263.CrossRefPubMed
5.
go back to reference Barbour AG: Antigenic variation of a relapsing fever Borrelia species. Annu Rev Microbiol. 1990, 44: 155-171. 10.1146/annurev.mi.44.100190.001103.CrossRefPubMed Barbour AG: Antigenic variation of a relapsing fever Borrelia species. Annu Rev Microbiol. 1990, 44: 155-171. 10.1146/annurev.mi.44.100190.001103.CrossRefPubMed
6.
go back to reference Barbour AG, Burman N, Carter CJ, Kitten T, Bergström S: Variable antigen genes of the relapsing fever agent Borrelia hermsii are activated by promoter addition. Mol Microbiol. 1991, 5: 489-493.CrossRefPubMed Barbour AG, Burman N, Carter CJ, Kitten T, Bergström S: Variable antigen genes of the relapsing fever agent Borrelia hermsii are activated by promoter addition. Mol Microbiol. 1991, 5: 489-493.CrossRefPubMed
7.
go back to reference Donelson JE: Mechanisms of antigenic variation in Borrelia hermsii and African trypanosomes. J Biol Chem. 1995, 270: 7783-7786.CrossRefPubMed Donelson JE: Mechanisms of antigenic variation in Borrelia hermsii and African trypanosomes. J Biol Chem. 1995, 270: 7783-7786.CrossRefPubMed
8.
go back to reference Restrepo BI, Carter CJ, Barbour AG: Activation of a vmp pseudogene in Borrelia hermsii: an alternate mechanism of antigenic variation during relapsing fever. Mol Microbiol. 1994, 13: 287-299.CrossRefPubMed Restrepo BI, Carter CJ, Barbour AG: Activation of a vmp pseudogene in Borrelia hermsii: an alternate mechanism of antigenic variation during relapsing fever. Mol Microbiol. 1994, 13: 287-299.CrossRefPubMed
9.
go back to reference Johnson WD: Borrelias species (relapsing fever). In Principles and practice of infectious diseases. Edited by: Mandell GL, Bennett JE, Dolin R. 1994, New York: Churchill Livingstone, 2141-2143. 4 Johnson WD: Borrelias species (relapsing fever). In Principles and practice of infectious diseases. Edited by: Mandell GL, Bennett JE, Dolin R. 1994, New York: Churchill Livingstone, 2141-2143. 4
10.
go back to reference Orloski K, Tharmaphornpilas P, O'Leary D, Ryan M, Schreifer M, Shoo R, et al: Epidemic louse-borne relapsing fever, Rumbek County, Sudan 1998–9. Am J Trop Med & Hyg. 1999, 61 (Supplement 3): 223-4. Abstract 173 Orloski K, Tharmaphornpilas P, O'Leary D, Ryan M, Schreifer M, Shoo R, et al: Epidemic louse-borne relapsing fever, Rumbek County, Sudan 1998–9. Am J Trop Med & Hyg. 1999, 61 (Supplement 3): 223-4. Abstract 173
11.
go back to reference Fekade D, Knox K, Hussein K, Melka A, Lalloo DG, Coxon RE, Warrell DA: Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor alpha. N Engl J Med. 1996, 335: 311-315. 10.1056/NEJM199608013350503.CrossRefPubMed Fekade D, Knox K, Hussein K, Melka A, Lalloo DG, Coxon RE, Warrell DA: Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor alpha. N Engl J Med. 1996, 335: 311-315. 10.1056/NEJM199608013350503.CrossRefPubMed
12.
go back to reference Negussie Y, Remick DG, DeForge LE, Kunkel SL, Eynon A, Griffin GE: Detection of plasma tumor necrosis factor, interleukins 6, and 8 during the Jarisch-Herxheimer Reaction of relapsing fever. J Exp Med. 1992, 175: 1207-1212.CrossRefPubMed Negussie Y, Remick DG, DeForge LE, Kunkel SL, Eynon A, Griffin GE: Detection of plasma tumor necrosis factor, interleukins 6, and 8 during the Jarisch-Herxheimer Reaction of relapsing fever. J Exp Med. 1992, 175: 1207-1212.CrossRefPubMed
13.
go back to reference Vidal V, Scragg IG, Cutler SJ, Rockett KA, Fekade D, Warrell DA, Wright DJ, Kwiatkowski D: Variable major lipoprotein is a principal TNF-inducing factor of louse-borne relapsing fever. Nat Med. 1998, 4: 1416-1420. 10.1038/4007.CrossRefPubMed Vidal V, Scragg IG, Cutler SJ, Rockett KA, Fekade D, Warrell DA, Wright DJ, Kwiatkowski D: Variable major lipoprotein is a principal TNF-inducing factor of louse-borne relapsing fever. Nat Med. 1998, 4: 1416-1420. 10.1038/4007.CrossRefPubMed
14.
go back to reference Cutler SJ, Fekade D, Hussein K, Knox KA, Melka A, Cann K, Emilianus AR, Warrell DA, Wright DJ: Successful in-vitro cultivation of Borrelia recurrentis. Lancet. 1994, 343: 242-10.1016/S0140-6736(94)91032-4.CrossRefPubMed Cutler SJ, Fekade D, Hussein K, Knox KA, Melka A, Cann K, Emilianus AR, Warrell DA, Wright DJ: Successful in-vitro cultivation of Borrelia recurrentis. Lancet. 1994, 343: 242-10.1016/S0140-6736(94)91032-4.CrossRefPubMed
15.
go back to reference Cutler SJ, Moss J, Fukunaga M, Wright DJ, Fekade D, Warrell D: Borrelia recurrentis characterization and comparison with relapsing-fever, Lyme-associated, and other Borrelia spp. Int J Syst Bacteriol. 1997, 47: 958-968.CrossRefPubMed Cutler SJ, Moss J, Fukunaga M, Wright DJ, Fekade D, Warrell D: Borrelia recurrentis characterization and comparison with relapsing-fever, Lyme-associated, and other Borrelia spp. Int J Syst Bacteriol. 1997, 47: 958-968.CrossRefPubMed
16.
go back to reference Fraser CM, Casjens S, Huang WM, Sutton GG, Clayton R, Lathigra R, White O, Ketchum KA, Dodson R, Hickey EK, Gwinn M, Dougherty B, Tomb JF, Fleischmann RD, Richardson D, Peterson J, Kerlavage AR, Quackenbush J, Salzberg S, Hanson M, van Vugt R, Palmer N, Adams MD, Gocayne J, Venter JC, et al: Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature. 1997, 390: 580-586. 10.1038/37551.CrossRefPubMed Fraser CM, Casjens S, Huang WM, Sutton GG, Clayton R, Lathigra R, White O, Ketchum KA, Dodson R, Hickey EK, Gwinn M, Dougherty B, Tomb JF, Fleischmann RD, Richardson D, Peterson J, Kerlavage AR, Quackenbush J, Salzberg S, Hanson M, van Vugt R, Palmer N, Adams MD, Gocayne J, Venter JC, et al: Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi. Nature. 1997, 390: 580-586. 10.1038/37551.CrossRefPubMed
18.
go back to reference Klein P, Somorjai RL, Lau PC: Distinctive properties of signal sequences from bacterial lipoproteins. Protein Eng. 1988, 2: 15-20.CrossRefPubMed Klein P, Somorjai RL, Lau PC: Distinctive properties of signal sequences from bacterial lipoproteins. Protein Eng. 1988, 2: 15-20.CrossRefPubMed
19.
go back to reference Estrem ST, Gaal T, Ross W, Gourse RL: Identification of an UP element consensus sequence for bacterial promoters. Proc Natl Acad Sci U S A. 1998, 95: 9761-9766. 10.1073/pnas.95.17.9761.CrossRefPubMedPubMedCentral Estrem ST, Gaal T, Ross W, Gourse RL: Identification of an UP element consensus sequence for bacterial promoters. Proc Natl Acad Sci U S A. 1998, 95: 9761-9766. 10.1073/pnas.95.17.9761.CrossRefPubMedPubMedCentral
20.
go back to reference Scragg IG, Kwiatkowski D, Vidal V, Reason A, Paxton T, Panico M, Dell A, Morris H: Structural Characterisation of the Inflammatory Moiety of a Variable Major Lipoprotein of Borrelia recurrentis. J Biol Chem. 2000, 275: 937-941. 10.1074/jbc.275.2.937.CrossRefPubMed Scragg IG, Kwiatkowski D, Vidal V, Reason A, Paxton T, Panico M, Dell A, Morris H: Structural Characterisation of the Inflammatory Moiety of a Variable Major Lipoprotein of Borrelia recurrentis. J Biol Chem. 2000, 275: 937-941. 10.1074/jbc.275.2.937.CrossRefPubMed
22.
go back to reference Pennington PM, Cadavid D, Bunikis J, Norris SJ, Barbour AG: Extensive interplasmidic duplications change the virulence phenotype of the relapsing fever agent Borrelia turicatae. Mol Microbiol. 1999, 34: 1120-1132. 10.1046/j.1365-2958.1999.01675.x.CrossRef Pennington PM, Cadavid D, Bunikis J, Norris SJ, Barbour AG: Extensive interplasmidic duplications change the virulence phenotype of the relapsing fever agent Borrelia turicatae. Mol Microbiol. 1999, 34: 1120-1132. 10.1046/j.1365-2958.1999.01675.x.CrossRef
23.
go back to reference Barbour AG, Carter CJ, Sohaskey CD: Surface protein variation by expression site switching in the relapsing fever agent Borrelia hermsii. Infect Immun. 2000, 68: 7114-7121. 10.1128/IAI.68.12.7114-7121.2000.CrossRefPubMedPubMedCentral Barbour AG, Carter CJ, Sohaskey CD: Surface protein variation by expression site switching in the relapsing fever agent Borrelia hermsii. Infect Immun. 2000, 68: 7114-7121. 10.1128/IAI.68.12.7114-7121.2000.CrossRefPubMedPubMedCentral
24.
go back to reference Schwan TG, Hinnebusch BJ: Bloodstream-versus tick-associated variants of a relapsing fever bacterium. Science. 1998, 280: 1938-1940. 10.1126/science.280.5371.1938.CrossRefPubMed Schwan TG, Hinnebusch BJ: Bloodstream-versus tick-associated variants of a relapsing fever bacterium. Science. 1998, 280: 1938-1940. 10.1126/science.280.5371.1938.CrossRefPubMed
25.
go back to reference Kitten T, Barbour AG: The relapsing fever agent Borrelia hermsii has multiple copies of its chromosome and linear plasmids. Genetics. 1992, 132: 311-32.PubMedPubMedCentral Kitten T, Barbour AG: The relapsing fever agent Borrelia hermsii has multiple copies of its chromosome and linear plasmids. Genetics. 1992, 132: 311-32.PubMedPubMedCentral
26.
go back to reference Sohaskey CD, Zuckert WR, Barbour AG: The extended promoters for two outer membrane lipoprotein genes of Borrelia spp. uniquely include a T-rich region. Mol Microbiol. 1999, 33: 41-51. 10.1046/j.1365-2958.1999.01443.x.CrossRefPubMed Sohaskey CD, Zuckert WR, Barbour AG: The extended promoters for two outer membrane lipoprotein genes of Borrelia spp. uniquely include a T-rich region. Mol Microbiol. 1999, 33: 41-51. 10.1046/j.1365-2958.1999.01443.x.CrossRefPubMed
27.
go back to reference Zhang JR, Norris SJ: Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion. Infect Immun. 1988, 66: 3698-3704. Zhang JR, Norris SJ: Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion. Infect Immun. 1988, 66: 3698-3704.
28.
go back to reference 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: 275-285. 10.1016/S0092-8674(00)80206-8.CrossRefPubMed 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: 275-285. 10.1016/S0092-8674(00)80206-8.CrossRefPubMed
29.
go back to reference Rudenko G, Blundell PA, Dirks Mulder A, Kieft R, Borst P: A ribosomal DNA promoter replacing the promoter of a telomeric VSG gene expression site can be efficiently switched on and off in T. brucei. Cell. 1995, 83: 547-553.CrossRefPubMed Rudenko G, Blundell PA, Dirks Mulder A, Kieft R, Borst P: A ribosomal DNA promoter replacing the promoter of a telomeric VSG gene expression site can be efficiently switched on and off in T. brucei. Cell. 1995, 83: 547-553.CrossRefPubMed
30.
go back to reference Barbour AG, Garon CF: Linear plasmids of the bacterium Borrelia burgdorferi have covalently closed ends. Science. 1987, 237: 409-411.CrossRefPubMed Barbour AG, Garon CF: Linear plasmids of the bacterium Borrelia burgdorferi have covalently closed ends. Science. 1987, 237: 409-411.CrossRefPubMed
31.
go back to reference Chomczynski P: A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques. 1993, 15: 532-537.PubMed Chomczynski P: A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques. 1993, 15: 532-537.PubMed
32.
go back to reference Sambrook J, Fitsch EF, Maniatis T: Molecular Cloning: A Laboratory Manual,. Cold Spring Harbor. 1989, Cold Spring Harbor Press, 2 Sambrook J, Fitsch EF, Maniatis T: Molecular Cloning: A Laboratory Manual,. Cold Spring Harbor. 1989, Cold Spring Harbor Press, 2
Metadata
Title
Characterisation of silent and active genes for a variable large protein of Borrelia recurrentis
Authors
Vincent Vidal
Sally Cutler
Ian G Scragg
David JM Wright
Dominic Kwiatkowski
Publication date
01-12-2002
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2002
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-2-25

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