title: The recombinant LIC10508 is a plasma fibronectin, plasminogen, fibrinogen and C4BP-binding protein of Leptospira interrogans.
abstract: Leptospirosis is a zoonosis caused by pathogenic Leptospira spp. In this study, we report that the recombinant proteins LIC10507, LIC10508 and LIC10509 are recognized by confirmed leptospirosis serum samples at both phases of the disease. The recombinant rLIC10508 and rLIC10507 are plasminogen (PLG)-binding proteins, capable of generating plasmin in the presence of a PLG activator. The proteins bind to PLG in a dose-dependent and saturable manner, fulfilling host-ligand interaction. Furthermore, rLIC10508 interacts with fibrinogen (Fg), plasma fibronectin and C4b binding protein (C4BP). The binding of rLIC10508 to Fg decreases the fibrin clotting in a thrombin-catalyzed reaction. The incubation with 4 μM of protein promoted 40% inhibition upon clotting formation. C4BP bound to rLIC10508 retained its cofactor activity for factor I promoting the cleavage of C4b protein, which may reduce the membrane attack complex formation. Although these proteins have high amino acid sequence similarity, rLIC10508 is the most talented of the three, a behavior that might be explained by its unique putative 3D structure, whereas structures of rLIC10507 and rLIC10509 are very similar. Plasmin generation (rLIC10507 and rLIC10508), together with decreasing fibrin clot formation (rLIC10508) and impairment of the complement system (rLIC10508) may help the bacteria to overcome host defense, facilitating the infection process.
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900, Sao Paulo, SP, Brazil.
authors.forename: Gabriela H
authors.initials: GH
authors.lastname: Siqueira
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900, Sao Paulo, SP, Brazil Programa de Pós-Graduação Interunidades em Biotecnologia, ICB, USP, Avenida Prof. Lineu Prestes, 1730, 05508-900, Sao Paulo, SP, Brazil.
authors.forename: Aline F
authors.initials: AF
authors.lastname: Teixeira
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900, Sao Paulo, SP, Brazil Programa de Pós-Graduação Interunidades em Biotecnologia, ICB, USP, Avenida Prof. Lineu Prestes, 1730, 05508-900, Sao Paulo, SP, Brazil.
authors.forename: Luis G
authors.initials: LG
authors.lastname: Fernandes
authors.affiliation: Laboratório de Zoonoses Bacterianas do VPS, Faculdade de MedicinaVeterinária e Zootecnia, USP, Avenida Prof. Dr. Orlando Marques de Paiva, 87, 05508-270, Sao Paulo, SP, Brazil.
authors.forename: Gisele O
authors.initials: GO
authors.lastname: de Souza
authors.affiliation: Nucleo de Estudos em Malária, Superintendência de Controle de Endemias-SUCEN/IMT-SP, USP, Av. Dr. Enéas de Carvalho Aguiar 470, CEP 05403-000, Sao Paulo, SP, Brazil.
authors.forename: Karin
authors.initials: K
authors.lastname: Kirchgatter
authors.affiliation: Centro de Bacteriologia, Instituto Adolfo Lutz, Avenida Dr. Arnaldo, 355, CEP 01246-902, Sao Paulo, Brazil.
authors.forename: Eliete C
authors.initials: EC
authors.lastname: Romero
authors.affiliation: Laboratório de Zoonoses Bacterianas do VPS, Faculdade de MedicinaVeterinária e Zootecnia, USP, Avenida Prof. Dr. Orlando Marques de Paiva, 87, 05508-270, Sao Paulo, SP, Brazil.
authors.forename: Silvio A
authors.initials: SA
authors.lastname: Vasconcellos
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900, Sao Paulo, SP, Brazil.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Vieira
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, 05503-900, Sao Paulo, SP, Brazil Programa de Pós-Graduação Interunidades em Biotecnologia, ICB, USP, Avenida Prof. Lineu Prestes, 1730, 05508-900, Sao Paulo, SP, Brazil ana.nascimento@butantan.gov.br.
authors.forename: Ana Lucia T O
authors.identifier: http://orcid.org/0000-0003-4851-0870
authors.initials: AL
authors.lastname: Nascimento
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D050716:Complement C4b-Binding Protein / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D007921:Leptospira interrogans / Q000378:metabolism*; D007922:Leptospirosis / Q000378:metabolism / Q000382:microbiology; D008958:Models, Molecular; D016366:Open Reading Frames; D010802:Phylogeny; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins; D017422:Sequence Analysis, DNA
chemical_list: D001425:Bacterial Outer Membrane Proteins; D050716:Complement C4b-Binding Protein; D005353:Fibronectins; D011994:Recombinant Proteins; D005340:Fibrinogen; D010958:Plasminogen; D005341:Fibrinolysin
keywords: C4BP; Leptospira; fibrinogen; host interactions; leptospirosis; plasmin