Characterization of the interaction of Leptospira interrogans with prothrombin/thrombin system and possible implications in virulence

• Grant number: 12/24164-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2013
• End date: June 30, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Ana Lucia Tabet Oller do Nascimento
• Grantee: Luis Guilherme Virgílio Fernandes
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated scholarship(s): 16/07680-5 - Construction of knock in mutants of saprophytic Leptospira biflexa and validation of leptospiral receptors, BE.EP.DR

Abstract

Leptospirosis is a global zoonosis recently included in the list of Tropical Neglected Diseases. In urban environments, rodents are the main reservoir of the disease, for allowing the colonization of leptospiras in the renal tubules and excreting them by urine. According to World Health Organization, the annual number of cases remains underestimated due to the broad spectra of symptoms that the patient may present, and also an inefficient rapid diagnostic kit. The situation worsens with the appearance of pulmonary hemorrhagic syndrome. There is no efficient vaccine until the moment. A better understanding of the bacterium pathogenesis may give us a start point for the development of an efficient vaccine. The molecular mechanisms underlying the appearance of hemorrhagic spots during severe leptospirosis are not yet understood, once leptospira hemolysins are unable to lyse human erythrocytes. Many pathogens interact with coagulation factor, including thrombin, a key enzyme on the coagulation processes. Thus, the project aims to study the interaction of the spirochete Lepotspira interrogans with the prothrombin/thrombin system, characterize this interaction, identify the protein(s) involved on this binding, evaluate the possible implications of this interaction in the bacterium pathogenesis. The immunoprotective effect of these thrombin-ligands proteins will also be evaluate.

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANTOS, JADSON V.; PEREIRA, PRISCILA R. M.; FERNANDES, LUIS G. V.; SIQUEIRA, GABRIELA HASE; DE SOUZA, GISELE O.; SOUZA FILHO, ANTONIO; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; CHAPOLA, ERICA G. B.; NASCIMENTO, ANA L. T. O.. Binding of human plasminogen by the lipoprotein LipL46 of Leptospira interrogans. MOLECULAR AND CELLULAR PROBES, v. 37, p. 12-21, FEB 2018. (12/24164-0, 14/50981-0, 15/02590-5)

PEREIRA, PRISCILA R. M.; FERNANDES, LUIS G. V.; DE SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; ROMERO, ELIETE C.; NASCIMENTO, ANA L. T. O.. Multifunctional and Redundant Roles of Leptospira interrogans Proteins in Bacterial-Adhesion and fibrin clotting inhibition. INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, v. 307, n. 6, p. 297-310, SEP 2017. (15/02590-5, 14/50981-0, 12/23913-9, 12/24164-0)

SIQUEIRA, GABRIELA H.; TEIXEIRA, ALINE F.; FERNANDES, LUIS G.; DE SOUZA, GISELE O.; KIRCHGATTER, KARIN; ROMERO, ELIETE C.; VASCONCELLOS, SILVIO A.; VIEIRA, MONICA L.; NASCIMENTO, ANA LUCIA T. O.. The recombinant LIC10508 is a plasma fibronectin, plasminogen, fibrinogen and C4BP-binding protein of Leptospira interrogans. PATHOGENS AND DISEASE, v. 74, n. 2, MAR 2016. (12/23913-9, 12/01797-7, 12/50523-7, 14/18337-4, 14/03792-8, 12/24164-0)

SILVA, LUCAS P.; FERNANDES, LUIS G. V.; VIEIRA, MONICA L.; DE SOUZA, GISELE O.; HEINEMANN, MARCOS B.; VASCONCELLOS, SILVIO A.; ROMERO, ELIETE C.; NASCIMENTO, ANA L. T. O.. Evaluation of two novel leptospiral proteins for their interaction with human host components. PATHOGENS AND DISEASE, v. 74, n. 5, JUL 2016. (14/50981-0, 14/18337-4, 12/23913-9, 12/24164-0)

FERNANDES, LUIS G. V.; FILHO, ANTONIO F. S.; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; ROMERO, ELIETE C.; NASCIMENTO, ANA L. T. O.. Decrease in antithrombin III and prothrombin serum levels contribute to coagulation disorders during leptospirosis. MICROBIOLOGY-SGM, v. 162, n. 8, p. 1407-1421, AUG 2016. (14/50981-0, 12/23913-9, 12/24164-0)

SANTOS, JADSON V.; PEREIRA, PRISCILA R. M.; FERNANDES, LUIS G. V.; SIQUEIRA, GABRIELA HASE; DE SOUZA, GISELE O.; SOUZA FILHO, ANTONIO; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; CHAPOLA, ERICA G. B.; NASCIMENTO, ANA L. T. O.. Binding of human plasminogen by the lipoprotein LipL46 of Leptospira interrogans. MOLECULAR AND CELLULAR PROBES, v. 37, p. 10-pg., 2018-02-01. (15/02590-5, 14/50981-0, 12/24164-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FERNANDES, Luis Guilherme Virgílio. Characterization of the interaction of Leptospira interrogans with prothrombin/thrombin system and possible implications in virulence.. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.