1887

Abstract

Lipoproteins are of great interest in understanding the molecular pathogenesis of spirochaetes. Because spirochaete lipobox sequences exhibit more plasticity than those of other bacteria, application of existing prediction algorithms to emerging sequence data has been problematic. In this paper a novel lipoprotein prediction algorithm is described, designated SpLip, constructed as a hybrid of a lipobox weight matrix approach supplemented by a set of lipoprotein signal peptide rules allowing for conservative amino acid substitutions. Both the weight matrix and the rules are based on a training set of 28 experimentally verified spirochaetal lipoproteins. The performance of the SpLip algorithm was compared to that of the hidden Markov model-based LipoP program and the rules-based algorithm Psort for all predicted protein-coding genes of sv. Copenhageni, sv. Lai, , , and . Psort sensitivity (13–35 %) was considerably less than that of SpLip (93–100 %) or LipoP (50–84 %) due in part to the requirement of Psort for Ala or Gly at the −1 position, a rule based on lipoproteins. The percentage of false-positive lipoprotein predictions by the LipoP algorithm (8–30 %) was greater than that of SpLip (0–1 %) or Psort (4–27 %), due in part to the lack of rules in LipoP excluding unprecedented amino acids such as Lys and Arg in the −1 position. This analysis revealed a higher number of predicted spirochaetal lipoproteins than was previously known. The improved performance of the SpLip algorithm provides a more accurate prediction of the complete lipoprotein repertoire of spirochaetes. The hybrid approach of supplementing weight matrix scoring with rules based on knowledge of protein secretion biochemistry may be a general strategy for development of improved prediction algorithms.

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2006-01-01
2020-08-13
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References

  1. Akins D. R, Purcell B. K, Mitra M. M, Norgard M. V, Radolf J. D. 1993; Lipid modification of the 17-kilodalton membrane immunogen of Treponema pallidum determines macrophage activation as well as amphiphilicity. Infect Immun61:1202–1210
    [Google Scholar]
  2. Aliprantis A. O, Yang R. B, Mark M. R, Suggett S, Devaux B, Radolf J. D, Klimpel G. R, Godowski P, Zychlinsky A. 1999; Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Science285:736–739[CrossRef]
    [Google Scholar]
  3. Bairoch A, Apweiler R. 2000; The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000. Nucleic Acids Res28:45–48[CrossRef]
    [Google Scholar]
  4. Barnett J. K, Barnett D, Bolin C. A, Summers T. A, Wagar E. A, Cheville N. F, Hartskeerl R. A, Haake D. A. 1999; Expression and distribution of leptospiral outer membrane components during renal infection of hamsters. Infect Immun67:853–861
    [Google Scholar]
  5. Braun V, Wolff H. 1970; The murein-lipoprotein linkage in the cell wall of Escherichia coli . Eur J Biochem14:387–391[CrossRef]
    [Google Scholar]
  6. Brightbill H. D, Libraty D. H, Krutzik S. R.24 other authors 1999; Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science285:732–736[CrossRef]
    [Google Scholar]
  7. Chamberlain N. R, Radolf J. D, Hsu P. L, Sell S, Norgard M. V. 1988; Genetic and physicochemical characterization of the recombinant DNA-derived 47-kilodalton surface immunogen of Treponema pallidum subsp. pallidum . Infect Immun56:71–78
    [Google Scholar]
  8. Cullen P. A, Coutts S. A, Cordwell S. J, Bulach D. M, Adler B. 2003a; Characterization of a locus encoding four paralogous outer membrane lipoproteins of Brachyspira hyodysenteriae . Microbes Infect5:275–283[CrossRef]
    [Google Scholar]
  9. Cullen P. A, Haake D. A, Bulach D. M, Zuerner R. L, Adler B. 2003b; LipL21 is a novel surface-exposed lipoprotein of pathogenic Leptospira species. Infect Immun71:2414–2421[CrossRef]
    [Google Scholar]
  10. Durbin R, Eddy S. R, Krogh A, Mitchison G. 1998; Biological Sequence Analysis. Probabilistic Models of Proteins and Nucleic Acids Cambridge: Cambridge University Press;
    [Google Scholar]
  11. Fraser C. M, Casjens S, Huang W. M.35 other authors 1997; Genomic sequence of a Lyme disease spirochaete, Borrelia burgdorferi . Nature390:580–586[CrossRef]
    [Google Scholar]
  12. Fraser C. M, Norris S. J, Weinstock G. M.29 other authors 1998; Complete genome sequence of Treponema pallidum , the syphilis spirochete. Science281:375–388[CrossRef]
    [Google Scholar]
  13. Glockner G, Lehmann R, Romualdi A, Pradella S, Schulte-Spechtel U, Schilhabel M, Wilske B, Suhnel J, Platzer M. 2004; Comparative analysis of the Borrelia garinii genome. Nucleic Acids Res32:6038–6046[CrossRef]
    [Google Scholar]
  14. Gonnet P, Rudd K. E, Lisacek F. 2004; Fine-tuning the prediction of sequences cleaved by signal peptidase II: a curated set of proven and predicted lipoproteins of Escherichia coli K-12. Proteomics4:1597–1613[CrossRef]
    [Google Scholar]
  15. Guo B. P, Brown E. L, Dorward D. W, Rosenberg L. C, Hook M. 1998; Decorin-binding adhesins from Borrelia burgdorferi . Mol Microbiol30:711–723[CrossRef]
    [Google Scholar]
  16. Haake D. A. 2000; Spirochaetal lipoproteins and pathogenesis. Microbiology146:1491–1504
    [Google Scholar]
  17. Haake D. A, Chao G, Zuerner R. L, Barnett J. K, Barnett D, Mazel M, Matsunaga J, Levett P. N, Bolin C. A. 2000; The leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection. Infect Immun68:2276–2285[CrossRef]
    [Google Scholar]
  18. Hellwage J, Meri T, Heikkila T, Alitalo A, Panelius J, Lahdenne P, Seppala I. J, Meri S. 2001; The complement regulator factor H binds to the surface protein OspE of Borrelia burgdorferi . J Biol Chem276:8427–8435[CrossRef]
    [Google Scholar]
  19. Howe T. R, Mayer L. W, Barbour A. G. 1985; A single recombinant plasmid expressing two major outer surface proteins of the Lyme disease spirochete. Science227:645–646[CrossRef]
    [Google Scholar]
  20. Juncker A. S, Willenbrock H, Von Heijne G, Brunak S, Nielsen H, Krogh A. 2003; Prediction of lipoprotein signal peptides in Gram-negative bacteria. Protein Sci12:1652–1662[CrossRef]
    [Google Scholar]
  21. Kornacki J. A, Oliver D. B. 1998; Lyme-disease-causing Borrelia species encode multiple lipoproteins homologous to peptide-binding proteins of ABC-type transporters. Infect Immun66:4115–4122
    [Google Scholar]
  22. Kyte J, Doolittle R. F. 1982; A simple method for displaying the hydropathic character of a protein. J Mol Biol157:105–132[CrossRef]
    [Google Scholar]
  23. Madan Babu M, Sankaran K. 2002; DOLOP – database of bacterial lipoproteins. Bioinformatics18:641–643[CrossRef]
    [Google Scholar]
  24. Matsunaga J, Barocchi M. A, Croda J.8 other authors 2003; Pathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily. Mol Microbiol49:929–945[CrossRef]
    [Google Scholar]
  25. Minamino T, Namba K. 2004; Self-assembly and type III protein export of the bacterial flagellum. J Mol Microbiol Biotechnol7:5–17[CrossRef]
    [Google Scholar]
  26. Mount D. W. 2001; Bioinformatics: Sequence and Genome Analysis: Cold Spring Harbor NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  27. Nakai K, Horton P. 1999; Psort: a program for detecting sorting signals in proteins and predicting their subcellular localization. Trends Biochem Sci24:34–36[CrossRef]
    [Google Scholar]
  28. Nascimento A. L, Ko A. I, Martins E. A.43 other authors 2004; Comparative genomics of two Leptospira interrogans serovars reveals novel insights into physiology and pathogenesis. J Bacteriol186:2164–2172[CrossRef]
    [Google Scholar]
  29. Paetzel M, Karla A, Strynadka N. C, Dalbey R. E. 2002; Signal peptidases. Chem Rev102:4549–4580[CrossRef]
    [Google Scholar]
  30. Probert W. S, Johnson B. J. 1998; Identification of a 47 kDa fibronectin-binding protein expressed by Borrelia burgdorferi isolate B31. Mol Microbiol30:1003–1015[CrossRef]
    [Google Scholar]
  31. Ren S. X, Fu G, Jiang X. G.36 other authors 2003; Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing. Nature422:888–893[CrossRef]
    [Google Scholar]
  32. Schwan T. G, Piesman J, Golde W. T, Dolan M. C, Rosa P. A. 1995; Induction of an outer surface protein on Borrelia burgdorferi during tick feeding. Proc Natl Acad Sci U S A92:2909–2913[CrossRef]
    [Google Scholar]
  33. Seshadri R, Myers G. S, Tettelin H.36 other authors 2004; Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes. Proc Natl Acad Sci U S A101:5646–5651[CrossRef]
    [Google Scholar]
  34. Shang E. S, Summers T. A, Haake D. A. 1996; Molecular cloning and sequence analysis of the gene encoding LipL41, a surface-exposed lipoprotein of pathogenic Leptospira species. Infect Immun64:2322–2330
    [Google Scholar]
  35. Stewart E. J, Katzen F, Beckwith J. 1999; Six conserved cysteines of the membrane protein DsbD are required for the transfer of electrons from the cytoplasm to the periplasm of Escherichia coli . EMBO J18:5963–5971[CrossRef]
    [Google Scholar]
  36. von Heijne G. 1989; The structure of signal peptides from bacterial lipoproteins. Protein Eng2:531–534[CrossRef]
    [Google Scholar]
  37. Zhang P, Cheng X, Duhamel G. E. 2000; Cloning and DNA sequence analysis of an immunogenic glucose-galactose MglB lipoprotein homologue from Brachyspira pilosicoli , the agent of colonic spirochetosis. Infect Immun68:4559–4565[CrossRef]
    [Google Scholar]
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