title: Evaluation of two novel leptospiral proteins for their interaction with human host components.
abstract: Pathogenic species of the genus Leptospira are the etiological agents of leptospirosis, the most widespread zoonosis. Mechanisms involved in leptospiral pathogenesis are not well understood. By data mining the genome sequences of Leptospira interrogans we have identified two proteins predicted to be surface exposed, LIC10821 and LIC10064. Immunofluorescence and proteinase K assays confirmed that the proteins are exposed. Reactivity of the recombinant proteins with human sera has shown that rLIC10821, but not rLIC10064, is recognized by antibodies in confirmed leptospirosis serum samples, suggesting its expression during infection. The rLIC10821 was able to bind laminin, in a dose-dependent fashion, and was called Lsa37 (leptospiral surface adhesin of 37 kDa). Studies with human plasma components demonstrated that rLIC10821 interacts with plasminogen (PLG) and fibrinogen (Fg). The binding of Lsa37 with PLG generates plasmin when PLG activator was added. Fibrin clotting reduction was observed in a thrombin-catalyzed reaction, when Fg was incubated with Lsa37, suggesting that this protein may interfere in the coagulation cascade during the disease. Although LIC10064 protein is more abundant than the corresponding Lsa37, binding activity with all the components tested was not detected. Thus, Lsa37 is a novel versatile adhesin that may mediate Leptospira-host interactions.
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil Programa de Pós-Graduação Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, USP, Avenida Prof. Lineu Prestes, 1730, 05508-900, São Paulo, SP, Brazil.
authors.forename: Lucas P
authors.initials: LP
authors.lastname: Silva
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil Programa de Pós-Graduação Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, USP, Avenida Prof. Lineu Prestes, 1730, 05508-900, São Paulo, SP, Brazil.
authors.forename: Luis G V
authors.initials: LG
authors.lastname: Fernandes
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Vieira
authors.affiliation: Laboratório de Zoonoses Bacterianas do VPS, Faculdade de Medicina Veterinária e Zootecnia, USP, Avenida Prof. Dr. Orlando Marques de Paiva, 87, 05508-270, São Paulo, SP, Brazil.
authors.forename: Gisele O
authors.initials: GO
authors.lastname: de Souza
authors.affiliation: Laboratório de Zoonoses Bacterianas do VPS, Faculdade de Medicina Veterinária e Zootecnia, USP, Avenida Prof. Dr. Orlando Marques de Paiva, 87, 05508-270, São Paulo, SP, Brazil.
authors.forename: Marcos B
authors.initials: MB
authors.lastname: Heinemann
authors.affiliation: Laboratório de Zoonoses Bacterianas do VPS, Faculdade de Medicina Veterinária e Zootecnia, USP, Avenida Prof. Dr. Orlando Marques de Paiva, 87, 05508-270, São Paulo, SP, Brazil.
authors.forename: Silvio A
authors.initials: SA
authors.lastname: Vasconcellos
authors.affiliation: Centro de Bacteriologia, Instituto Adolfo Lutz, Avenida Dr. Arnaldo, 355, CEP 01246-902, São Paulo, SP, Brazil.
authors.forename: Eliete C
authors.initials: EC
authors.lastname: Romero
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil Programa de Pós-Graduação Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, USP, Avenida Prof. Lineu Prestes, 1730, 05508-900, São Paulo, SP, Brazil ana.nascimento@butantan.gov.br.
authors.forename: Ana L T O
authors.initials: AL
authors.lastname: Nascimento
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D019295:Computational Biology / Q000379:methods; D005340:Fibrinogen / Q000378:metabolism; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D007797:Laminin / Q000378:metabolism; D007919:Leptospira / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D007922:Leptospirosis / Q000378:metabolism* / Q000382:microbiology*; D016366:Open Reading Frames; D010802:Phylogeny; D011485:Protein Binding; D021381:Protein Transport; D059748:Proteolysis; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D001426:Bacterial Proteins; D007797:Laminin; D011994:Recombinant Proteins; D005340:Fibrinogen
keywords: Leptospira; adhesion; fibrin reduction; leptospirosis; plasmin