The recombinant LIC10508 is a plasma fibronectin, plasminogen, fibrinogen and C4BP-binding protein of Leptospira interrogans

Author(s)

Siqueira, Gabriela H. ^[1] ; Teixeira, Aline F. ^{[1, 2]} ; Fernandes, Luis G. ^{[1, 2]} ; de Souza, Gisele O. ^[3] ; Kirchgatter, Karin ^[4] ; Romero, Eliete C. ^[5] ; Vasconcellos, Silvio A. ^[3] ; Vieira, Monica L. ^[1] ; Nascimento, Ana Lucia T. O. ^{[1, 2]}

Affiliation

^[1] Inst Butantan, Ctr Biotecnol, Ave Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, ICB, Programa Posgrad Interunidades Biotecnol, Ave Prof Lineu Prestes 1730, BR-05503900 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Fac Med Vet & Zootecnia, Lab Zoonoses Bacterianas VPS, Ave Prof Dr Orlando Marques de Paiva 87, BR-05508270 Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Superintendencia Controle Endemias SUCEN IMT SP, Nucleo Estudos Malaria, Av Dr Eneas de Carvalho Aguiar 470, BR-05403000 Sao Paulo, SP - Brazil

^[5] Adolfo Lutz Inst, Ctr Bacteriol, Ave Dr Arnaldo 355, BR-01246902 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: PATHOGENS AND DISEASE; v. 74, n. 2 MAR 2016.
• Web of Science Citations: 3

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 mu M 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. (AU)

• FAPESP's process: 12/23913-9 - Indentification and characterization of proteins of Leptospira interrogans involved in host-pathogen interactions
• Grantee: Ana Lucia Tabet Oller do Nascimento
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/01797-7 - Evaluation and characterization of vaccine candidates against leptospirosis
• Grantee: Aline Florencio Teixeira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/50523-7 - Cloning, expression, purification and characterization of Leptospira interrogans thermolysin: interactions with plasminogen / plasmin system and implications for infection
• Grantee: Mônica Larucci Vieira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/18337-4 - Modulação da coagulação e inflamação do hospedeiro por Leptospira
• Grantee: Mônica Larucci Vieira
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 14/03792-8 - "Evaluation of the immune evasion by pathogenic Leptospira interrogans at the terminal complement system pathway level"
• Grantee: Gabriela Hase Siqueira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/24164-0 - Characterization of the interaction of Leptospira interrogans with prothrombin/thrombin system and possible implications in virulence
• Grantee: Luis Guilherme Virgílio Fernandes
• Support Opportunities: Scholarships in Brazil - Doctorate