1921
Volume 89, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

We report cloning, expression, purification, and characterization of three predicted leptospiral membrane proteins (LIC11360, LIC11009, and LIC11975). analysis and proteinase K accessibility data suggest that these proteins might be surface exposed. We show that proteins encoded by LIC11360, LIC11009 and LIC11975 genes interact with laminin in a dose-dependent and saturable manner. The proteins are referred to as leptospiral urface adhesions 23, 26, and 36 (Lsa23, Lsa26, and Lsa36), respectively. These proteins also bind plasminogen and generate active plasmin. Attachment of Lsa23 and Lsa36 to fibronectin occurs through the involvement of the 30-kDa and 70-kDa heparin-binding domains of the ligand. Dose-dependent, specific-binding of Lsa23 to the complement regulator C4BP and to a lesser extent, to factor H, suggests that this protein may interfere with the complement cascade pathways. spp. may use these interactions as possible mechanisms during the establishment of infection.

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2013-12-04
2017-09-20
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References

  1. Bharti AR, Nally JE, Ricaldi JN, Matthias MA, Diaz MM, Lovett MA, Levett PN, Gilman RH, Willig MR, Gotuzzo E, Vinetz JM, , 2003. Leptospirosis: a zoonotic disease of global importance. Lancet Infect Dis 3: 757771.[Crossref]
  2. de la Pena-Moctezuma A, Bulach DM, Adler B, , 2001. Genetic differences among the LPS biosynthetic loci of serovars of Leptospira interrogans and Leptospira borgpetersenii . FEMS Immunol Med Microbiol 31: 7381.[Crossref]
  3. Faine S, Adler B, Bolin C, Perolat P, , 1999. Leptospira and Leptospirosis. Melbourne, Australia: MediSci Press.
  4. Nakai K, Kanehisa M, , 1991. Expert system for predicting protein localization sites in gram-negative bacteria. Proteins 11: 95110.[Crossref]
  5. Juncker AS, Willenbrock H, Von Heijne G, Brunak S, Nielsen H, Krogh A, , 2003. Prediction of lipoprotein signal peptides in gram-negative bacteria. Protein Sci 12: 16521662.[Crossref]
  6. Nascimento AL, Ko AI, Martins EA, Monteiro-Vitorello CB, Ho PL, Haake DA, Verjovski-Almeida S, Hartskeerl RA, Marques MV, Oliveira MC, Menck CF, Leite LC, Carrer H, Coutinho LL, Degrave WM, Dellagostin OA, El-Dorry H, Ferro ES, Ferro MI, Furlan LR, Gamberini M, Giglioti EA, Goes-Neto A, Goldman GH, Goldman MH, Harakava R, Jeronimo SM, Junqueira-de-Azevedo IL, Kimura ET, Kuramae EE, Lemos EG, Lemos MV, Marino CL, Nunes LR, de Oliveira RC, Pereira GG, Reis MS, Schriefer A, Siqueira WJ, Sommer P, Tsai SM, Simpson AJ, Ferro JA, Camargo LE, Kitajima JP, Setubal JC, Van Sluys MA, , 2004. Comparative genomics of two Leptospira interrogans serovars reveals novel insights into physiology and pathogenesis. J Bacteriol 186: 21642172.[Crossref]
  7. Nascimento AL, Verjovski-Almeida S, Van Sluys MA, Monteiro-Vitorello CB, Camargo LE, Digiampietri LA, Harstkeerl RA, Ho PL, Marques MV, Oliveira MC, Setubal JC, Haake DA, Martins EA, , 2004. Genome features of Leptospira interrogans serovar Copenhageni. Braz J Med Biol Res 37: 459477.[Crossref]
  8. Fernandes LG, Vieira ML, Kirchgatter K, Alves IJ, de Morais ZM, Vasconcellos SA, Romero EC, Nascimento AL, , 2012. OmpL1 is an extracellular matrix- and plasminogen-interacting protein of Leptospira spp. Infect Immun 80: 36793692.[Crossref]
  9. Atzingen MV, Gomez RM, Schattner M, Pretre G, Goncales AP, de Morais ZM, Vasconcellos SA, Nascimento AL, , 2009. Lp95, a novel leptospiral protein that binds extracellular matrix components and activates e-selectin on endothelial cells. J Infect 59: 264276.[Crossref]
  10. Barbosa AS, Abreu PA, Neves FO, Atzingen MV, Watanabe MM, Vieira ML, Morais ZM, Vasconcellos SA, Nascimento AL, , 2006. A newly identified leptospiral adhesin mediates attachment to laminin. Infect Immun 74: 63566364.[Crossref]
  11. Atzingen MV, Barbosa AS, De Brito T, Vasconcellos SA, de Morais ZM, Lima DM, Abreu PA, Nascimento AL, , 2008. Lsa21, a novel leptospiral protein binding adhesive matrix molecules and present during human infection. BMC Microbiol 8: 70.[Crossref]
  12. Longhi MT, Oliveira TR, Romero EC, Goncales AP, de Morais ZM, Vasconcellos SA, Nascimento AL, , 2009. A newly identified protein of Leptospira interrogans mediates binding to laminin. J Med Microbiol 58: 12751282.[Crossref]
  13. Vieira ML, de Morais ZM, Goncales AP, Romero EC, Vasconcellos SA, Nascimento AL, , 2010. Lsa63, a newly identified surface protein of Leptospira interrogans binds laminin and collagen IV. J Infect 60: 5264.[Crossref]
  14. Oliveira TR, Longhi MT, Goncales AP, de Morais ZM, Vasconcellos SA, Nascimento AL, , 2010. LipL53, a temperature regulated protein from Leptospira interrogans that binds to extracellular matrix molecules. Microbes Infect 12: 207217.[Crossref]
  15. Oliveira R, de Morais ZM, Goncales AP, Romero EC, Vasconcellos SA, Nascimento AL, , 2011. Characterization of novel OmpA-like protein of Leptospira interrogans that binds extracellular matrix molecules and plasminogen. PLoS ONE 6: e21962.[Crossref]
  16. Mendes RS, Von Atzingen M, de Morais ZM, Goncales AP, Serrano SM, Asega AF, Romero EC, Vasconcellos SA, Nascimento AL, , 2011. The novel leptospiral surface adhesin Lsa20 binds laminin and human plasminogen and is probably expressed during infection. Infect Immun 79: 46574667.[Crossref]
  17. Domingos RF, Vieira ML, Romero EC, Goncales AP, de Morais ZM, Vasconcellos SA, Nascimento AL, , 2012. Features of two proteins of Leptospira interrogans with potential role in host-pathogen interactions. BMC Microbiol 12: 50.[Crossref]
  18. Souza NM, Vieira ML, Alves IJ, de Morais ZM, Vasconcellos SA, Nascimento AL, , 2012. Lsa30, a novel adhesin of Leptospira interrogans binds human plasminogen and the complement regulator C4bp. Microb Pathog 53: 125134.[Crossref]
  19. Vieira ML, Vasconcellos SA, Goncales AP, de Morais ZM, Nascimento AL, , 2009. Plasminogen acquisition and activation at the surface of Leptospira species lead to fibronectin degradation. Infect Immun 77: 40924101.[Crossref]
  20. Vieira ML, Atzingen MV, Oliveira TR, Oliveira R, Andrade DM, Vasconcellos SA, Nascimento AL, , 2010. In vitro identification of novel plasminogen-binding receptors of the pathogen Leptospira interrogans . PLoS ONE 5: e11259.[Crossref]
  21. Turner LH, , 1970. Leptospirosis. 3. Maintenance, isolation and demonstration of leptospires. Trans R Soc Trop Med Hyg 64: 623646.[Crossref]
  22. Yu CS, Lin CJ, Hwang JK, , 2004. Predicting subcellular localization of proteins for gram-negative bacteria by support vector machines based on n-peptide compositions. Protein Sci 13: 14021406.[Crossref]
  23. Letunic I, Copley RR, Pils B, Pinkert S, Schultz J, Bork P, , 2006. SMART 5: domains in the context of genomes and networks. Nucleic Acids Res 34: D257D260.[Crossref]
  24. Finn RD, Mistry J, Schuster-Bockler B, Griffiths-Jones S, Hollich V, Lassmann T, Moxon S, Marshall M, Khanna A, Durbin R, Eddy SR, Sonnhammer EL, Bateman A, , 2006. Pfam: clans, web tools and services. Nucleic Acids Res 34: D247D251.[Crossref]
  25. Bendtsen JD, Nielsen H, von Heijne G, Brunak S, , 2004. Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340: 783795.[Crossref]
  26. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ, , 1997. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25: 33893402.[Crossref]
  27. Marchler-Bauer A, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott C, Fong JH, Geer LY, Geer RC, Gonzales NR, Gwadz M, He S, Hurwitz DI, Jackson JD, Ke Z, Lanczycki CJ, Liebert CA, Liu C, Lu F, Lu S, Marchler GH, Mullokandov M, Song JS, Tasneem A, Thanki N, Yamashita RA, Zhang D, Zhang N, Bryant SH, , 2009. CDD: specific functional annotation with the Conserved Domain Database. Nucleic Acids Res 37: D205D210.[Crossref]
  28. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG, , 2007. Clustal W and Clustal X version 2.0. Bioinformatics 23: 29472948.[Crossref]
  29. Ramos CR, Abreu PA, Nascimento AL, Ho PL, , 2004. A high-copy T7 Escherichia coli expression vector for the production of recombinant proteins with a minimal N-terminal His-tagged fusion peptide. Braz J Med Biol Res 37: 11031109.[Crossref]
  30. Bhandari P, Gowrishankar J, , 1997. An Escherichia coli host strain useful for efficient overproduction of cloned gene products with NaCl as the inducer. J Bacteriol 179: 44034406.[Crossref]
  31. Louis-Jeune C, Andrade-Navarro MA, Perez-Iratxeta C, , 2012. Prediction of protein secondary structure from circular dichroism using theoretically derived spectra. Proteins 80: 374381.[Crossref]
  32. Oliveira TR, Longhi MT, de Morais ZM, Romero EC, Blanco RM, Kirchgatter K, Vasconcellos SA, Nascimento AL, , 2008. Evaluation of leptospiral recombinant antigens MPL17 and MPL21 for serological diagnosis of leptospirosis by enzyme-linked immunosorbent assays. Clin Vaccine Immunol 15: 17151722.[Crossref]
  33. Flannery B, Costa D, Carvalho FP, Guerreiro H, Matsunaga J, Da Silva ED, Ferreira AG, Riley LW, Reis MG, Haake DA, Ko AI, , 2001. Evaluation of recombinant Leptospira antigen-based enzyme-linked immunosorbent assays for the serodiagnosis of leptospirosis. J Clin Microbiol 39: 33033310.[Crossref]
  34. Haake DA, Chao G, Zuerner RL, Barnett JK, Barnett D, Mazel M, Matsunaga J, Levett PN, Bolin CA, , 2000. The leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection. Infect Immun 68: 22762285.[Crossref]
  35. Stamm LV, Gherardini FC, Parrish EA, Moomaw CR, , 1991. Heat shock response of spirochetes. Infect Immun 59: 15721575.
  36. Lin YP, Lee DW, McDonough SP, Nicholson LK, Sharma Y, Chang YF, , 2009. Repeated domains of Leptospira immunoglobulin-like proteins interact with elastin and tropoelastin. J Biol Chem 284: 1938019391.[Crossref]
  37. Altschul SF, Wootton JC, Gertz EM, Agarwala R, Morgulis A, Schaffer AA, Yu YK, , 2005. Protein database searches using compositionally adjusted substitution matrices. FEBS J 272: 51015109.[Crossref]
  38. Malmstrom J, Beck M, Schmidt A, Lange V, Deutsch EW, Aebersold R, , 2009. Proteome-wide cellular protein concentrations of the human pathogen Leptospira interrogans . Nature 460: 762765.[Crossref]
  39. Pinne M, Haake DA, , 2009. A comprehensive approach to identification of surface-exposed, outer membrane-spanning proteins of Leptospira interrogans . PLoS ONE 4: e6071.[Crossref]
  40. Vieira ML, Atzingen MV, Oliveira R, Mendes RS, Domingos RF, Vasconcellos SA, Nascimento AL, , 2012. Plasminogen binding proteins and plasmin generation on the surface of Leptospira spp.: the contribution to the bacteria-host interactions. J Biomed Biotechnol. doi:10.1155/2012/758513. Epub 2012 Oct 15.
  41. Lahteenmaki K, Kuusela P, Korhonen TK, , 2001. Bacterial plasminogen activators and receptors. FEMS Microbiol Rev 25: 531552.[Crossref]
  42. Seib KL, Zhao X, Rappuoli R, , 2012. Developing vaccines in the era of genomics: a decade of reverse vaccinology. Clin Microbiol Infect 18 (Suppl 5): 109116.[Crossref]
  43. Schneider MC, Exley RM, Chan H, Feavers I, Kang YH, Sim RB, Tang CM, , 2006. Functional significance of factor H binding to Neisseria meningitidis . J Immunol 176: 75667575.[Crossref]
  44. Hava DL, Camilli A, , 2002. Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors. Mol Microbiol 45: 13891406.
  45. Ljungh A, Wadstrom T, , 1996. Interactions of bacterial adhesins with the extracellular matrix. Adv Exp Med Biol 408: 129140.[Crossref]
  46. Stevenson B, Choy HA, Pinne M, Rotondi ML, Miller MC, Demoll E, Kraiczy P, Cooley AE, Creamer TP, Suchard MA, Brissette CA, Verma A, Haake DA, , 2007. Leptospira interrogans endostatin-like outer membrane proteins bind host fibronectin, laminin and regulators of complement. PLoS ONE 2: e1188.[Crossref]
  47. Carvalho E, Barbosa AS, Gomez RM, Cianciarullo AM, Hauk P, Abreu PA, Fiorini LC, Oliveira ML, Romero EC, Goncales AP, Morais ZM, Vasconcellos SA, Ho PL, , 2009. Leptospiral TlyC is an extracellular matrix-binding protein and does not present hemolysin activity. FEBS Lett.
  48. Pinne M, Choy HA, Haake DA, , 2010. The OmpL37 surface-exposed protein is expressed by pathogenic Leptospira during infection and binds skin and vascular elastin. PLoS Negl Trop Dis 4: e815.[Crossref]
  49. Coleman JL, Benach JL, , 1999. Use of the plasminogen activation system by microorganisms. J Lab Clin Med 134: 567576.[Crossref]
  50. Coleman JL, Benach JL, , 2000. The generation of enzymatically active plasmin on the surface of spirochetes. Methods 21: 133141.[Crossref]
  51. Nordstrand A, Shamaei-Tousi A, Ny A, Bergstrom S, , 2001. Delayed invasion of the kidney and brain by Borrelia crocidurae in plasminogen-deficient mice. Infect Immun 69: 58325839.[Crossref]
  52. Haile WB, Coleman JL, Benach JL, , 2006. Reciprocal upregulation of urokinase plasminogen activator and its inhibitor, PAI-2, by Borrelia burgdorferi affects bacterial penetration and host-inflammatory response. Cell Microbiol 8: 13491360.[Crossref]
  53. Ponting CP, Marshall JM, Cederholm-Williams SA, , 1992. Plasminogen: a structural review. Blood Coagul Fibrinolysis 3: 605614.[Crossref]
  54. Angles-Cano E, Rouy D, Lijnen HR, , 1992. Plasminogen binding by alpha 2-antiplasmin and histidine-rich glycoprotein does not inhibit plasminogen activation at the surface of fibrin. Biochim Biophys Acta 1156: 3442.[Crossref]
  55. Verma A, Brissette CA, Bowman AA, Shah ST, Zipfel PF, Stevenson B, , 2010. Leptospiral endostatin-like protein A is a bacterial cell surface receptor for human plasminogen. Infect Immun 78: 20532059.[Crossref]
  56. Lindahl G, Sjobring U, Johnsson E, , 2000. Human complement regulators: a major target for pathogenic microorganisms. Curr Opin Immunol 12: 4451.[Crossref]
  57. Blom AM, , 2002. Structural and functional studies of complement inhibitor C4b-binding protein. Biochem Soc Trans 30: 978982.[Crossref]
  58. Gigli I, Fujita T, Nussenzweig V, , 1979. Modulation of the classical pathway C3 convertase by plasma proteins C4 binding protein and C3b inactivator. Proc Natl Acad Sci USA 76: 65966600.[Crossref]
  59. Berggard K, Johnsson E, Mooi FR, Lindahl G, , 1997. Bordetella pertussis binds the human complement regulator C4BP: role of filamentous hemagglutinin. Infect Immun 65: 36383643.
  60. Ram S, Cullinane M, Blom AM, Gulati S, McQuillen DP, Monks BG, O'Connell C, Boden R, Elkins C, Pangburn MK, Dahlback B, Rice PA, , 2001. Binding of C4b-binding protein to porin: a molecular mechanism of serum resistance of Neisseria gonorrhoeae . J Exp Med 193: 281295.[Crossref]
  61. Thern A, Stenberg L, Dahlback B, Lindahl G, , 1995. Ig-binding surface proteins of Streptococcus pyogenes also bind human C4b-binding protein (C4BP), a regulatory component of the complement system. J Immunol 154: 375386.
  62. Meri T, Murgia R, Stefanel P, Meri S, Cinco M, , 2005. Regulation of complement activation at the C3-level by serum resistant leptospires. Microb Pathog 39: 139147.[Crossref]
  63. Castiblanco-Valencia MM, Fraga TR, Silva LB, Monaris D, Abreu PA, Strobel S, Jozsi M, Isaac L, Barbosa AS, , 2012. Leptospiral immunoglobulin-like proteins interact with human complement regulators factor H, FHL-1, FHR-1, and C4BP. J Infect Dis 205: 9951004.[Crossref]
  64. Barbosa AS, Monaris D, Silva LB, Morais ZM, Vasconcellos SA, Cianciarullo AM, Isaac L, Abreu PA, , 2012. Functional characterization of LcpA, a surface-exposed protein of Leptospira spp. that binds the human complement regulator C4BP. Infect Immun 78: 32073216.[Crossref]
  65. Verma A, Hellwage J, Artiushin S, Zipfel PF, Kraiczy P, Timoney JF, Stevenson B, , 2006. LfhA, a novel factor H-binding protein of Leptospira interrogans . Infect Immun 74: 26592666.[Crossref]
  66. Choy HA, , 2012. Multiple activities of LigB potentiate virulence of Leptospira interrogans: inhibition of alternative and classical pathways of complement. PLoS ONE 7: e41566.[Crossref]
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  • Received : 19 Apr 2013
  • Accepted : 18 Jul 2013

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