Lysine-dependent multipoint binding of the Borrelia burgdorferi virulence factor outer surface protein E to the C terminus of factor H

被引:58
作者
Alitalo, A
Meri, T
Chen, T
Lankinen, H
Cheng, ZZ
Jokiranta, TS
Seppälä, KJT
Lahdenne, P
Hefty, PS
Akins, DR
Meri, S
机构
[1] Haartman Inst, Dept Bacteriol & Immunol, FIN-00014 Helsinki, Finland
[2] Univ Helsinki, Cent Hosp, Helsinki, Finland
[3] Univ Helsinki, Peptide & Prot Lab, Haartman Inst, Helsinki, Finland
[4] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK USA
关键词
D O I
10.4049/jimmunol.172.10.6195
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Serum resistance, an important virulence determinant of Borrelia burgdorferi sensu lato strains belonging to the Borrelia afzelii and B. burgdorferi sensu stricto genotypes, is related to binding of the complement inhibitor factor H to the spirochete surface protein outer surface protein E (OspE) and its homologues. In this study, we show that the C-terminal short consensus repeats 18-20 of both human and mouse factor H bind to OspE. Analogously, factor H-related protein 1, a distinct plasma protein with three short consensus repeat domains homologous to those in factor H, bound to OspE. Deleting 15-aa residues (region V) from the C terminus of the OspE paralog P21 (a 20.7-kDa OspE-paralogous surface lipoprotein in the B. burgdorferi sensu stricto 297 strain) abolished factor H binding. However, C-terminal peptides from OspE, P21, or OspEF-related protein P alone and the C-terminal deletion mutants of P21 inhibited factor H binding to OspE only partially when compared with full-length P21 or its N-terminal mutant. Alanine substitution of amino acids in peptides from the key binding regions of the OspE family indicated that several lysine residues are required for factor H binding. Thus, the borrelial OspE family proteins bind the C inhibitor factor H via multiple sites in a lysine-dependent manner. The C-terminal site V (Ala(151)-Lys(166)) is necessary, but not sufficient, for factor H binding in both rodents and humans. Identification of the necessary binding sites forms a basis for the development of vaccines that block the factor H-OspE interaction and thereby promote the killing of Borreliae.
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页码:6195 / 6201
页数:7
相关论文
共 45 条
  • [1] Why is chronic Lyme borreliosis chronic?
    Aberer, E
    Koszik, F
    Silberer, M
    [J]. CLINICAL INFECTIOUS DISEASES, 1997, 25 : S64 - S70
  • [2] Molecular and evolutionary analysis of Borrelia burgdorferi 297 circular plasmid-encoded lipoproteins with OspE- and OspF-like leader peptides
    Akins, DR
    Caimano, MJ
    Yang, HF
    Cerna, F
    Norgard, MV
    Radolf, JD
    [J]. INFECTION AND IMMUNITY, 1999, 67 (03) : 1526 - 1532
  • [3] LIPID MODIFICATION OF THE 17-KILODALTON MEMBRANE IMMUNOGEN OF TREPONEMA-PALLIDUM DETERMINES MACROPHAGE ACTIVATION AS WELL AS AMPHIPHILICITY
    AKINS, DR
    PURCELL, BK
    MITRA, MM
    NORGARD, MV
    RADOLF, JD
    [J]. INFECTION AND IMMUNITY, 1993, 61 (04) : 1202 - 1210
  • [4] New animal model for studying Lyme disease spirochetes in a mammalian host-adapted state
    Akins, DR
    Bourell, KW
    Caimano, MJ
    Norgard, MV
    Radolf, JD
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (10) : 2240 - 2250
  • [5] Complement inhibitor factor H binding to Lyme disease spirochetes is mediated by inducible expression of multiple plasmid-encoded outer surface protein E paralogs
    Alitalo, A
    Meri, T
    Lankinen, H
    Seppälä, L
    Lahdenne, P
    Hefty, PS
    Akins, D
    Meri, S
    [J]. JOURNAL OF IMMUNOLOGY, 2002, 169 (07) : 3847 - 3853
  • [6] Complement evasion by Borrelia burgdorferi:: Serum-resistant strains promote C3b inactivation
    Alitalo, A
    Meri, T
    Rämö, L
    Jokiranta, TS
    Heikkilä, T
    Seppälä, IJT
    Oksi, J
    Viljanen, M
    Meri, S
    [J]. INFECTION AND IMMUNITY, 2001, 69 (06) : 3685 - 3691
  • [7] Streptococcal β protein has separate binding sites for human factor H and IgA-Fc
    Areschoug, T
    Stålhammar-Carlemalm, M
    Karlsson, I
    Lindahl, G
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (15) : 12642 - 12648
  • [8] Blackmore TK, 1998, J IMMUNOL, V160, P3342
  • [9] LYME-DISEASE - A TICK-BORNE SPIROCHETOSIS
    BURGDORFER, W
    BARBOUR, AG
    HAYES, SF
    BENACH, JL
    GRUNWALDT, E
    DAVIS, JP
    [J]. SCIENCE, 1982, 216 (4552) : 1317 - 1319
  • [10] A bacterial genome in flux:: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi
    Casjens, S
    Palmer, N
    van Vugt, R
    Huang, WM
    Stevenson, B
    Rosa, P
    Lathigra, R
    Sutton, G
    Peterson, J
    Dodson, RJ
    Haft, D
    Hickey, E
    Gwinn, M
    White, O
    Fraser, CM
    [J]. MOLECULAR MICROBIOLOGY, 2000, 35 (03) : 490 - 516