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Indentification and characterization of proteins of Leptospira interrogans involved in host-pathogen interactions

Grant number: 12/23913-9
Support type:Regular Research Grants
Duration: April 01, 2013 - December 31, 2015
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Ana Lucia Tabet Oller Do Nascimento
Grantee:Ana Lucia Tabet Oller Do Nascimento
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Leptospirosis is an important global zoonosis that has been recently considered a neglected tropical disease. According to the World Health Organization, the number of annual clinical cases remains underestimated due to the wide spectrum of symptoms presented by patients and the lack of an efficient diagnostic. To date, there is not a good protective vaccine. The identification of outer membrane proteins, well conserved among pathogenic leptospiral strains, is the main focus of the currently research to elucidate mechanisms of pathogenesis. These proteins are most probably involved in the interactions of leptospires with the external environmental, and may act as targets for the host immune system. By employing the genome sequences of Leptospira interrogans and bioinformatics tools, our group has identified several membrane proteins that interact with extracellular matrix (ECM) components with possible role in the bacterial adhesion, proteins that interact with fibrinolytic system plasminogen/plasmin (PLG/PLA) and could act in the invasion process, and proteins that bind complement regulators and may participate in the leptospiral immune evasion. Considering the above stated, the present project aims: (i) identification, cloning, protein expression and purification of six novel predicted membrane proteins; these proteins will be characterized for their immunogenic activities in animal model and their interactions with ECM and serum host components; (ii) analysis of possible implications of PLA generation within bacterial surface; (iii) evaluation of interaction of leptospires and recombinant proteins with serum fibrinogen and implications for the fibrin (clot) formation, bearing in mind that severe leptospirosis produces multiple hemorrhage focus. (AU)

Scientific publications (11)
(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)
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. Web of Science Citations: 6.
FERNANDES, LUIS G. V.; TEIXEIRA, ALINE F.; FILHO, ANTONIO F. S.; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; ROMERO, ELIETE C.; NASCIMENTO, ANA L. T. O. Immune response and protective profile elicited by a multi-epitope chimeric protein derived from Leptospira interrogans. INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, v. 57, p. 61-69, APR 2017. Web of Science Citations: 9.
VIEIRA, MONICA L.; DE ANDRADE, SONIA A.; MORAIS, ZENAIDE M.; VASCONCELLOS, SILVIO A.; DAGLI, MARIA LUCIA Z.; NASCIMENTO, ANA LUCIA T. O. Leptospira Infection Interferes with the Prothrombinase Complex Assembly during Experimental Leptospirosis. FRONTIERS IN MICROBIOLOGY, v. 8, MAR 28 2017. Web of Science Citations: 0.
FIGUEREDO, JUPCIANA M.; SIQUEIRA, GABRIELA H.; DE SOUZA, GISELE O.; HEINEMANN, MARCOS B.; VASCONCELLOS, SILVIO A.; CHAPOLA, ERICA G. B.; NASCIMENTO, ANA L. T. O. Characterization of two new putative adhesins of Leptospira interrogans. MICROBIOLOGY-SGM, v. 163, n. 1, p. 37-51, JAN 2017. Web of Science Citations: 3.
COSATE, MARIA RAQUEL; SIQUEIRA, GABRIELA HASE; DE SOUZA, GISELE OLIVEIRA; VASCONCELLOS, SILVIO ARRUDA; NASCIMENTO, ANA LUCIA T. O. Mammalian cell entry (Mce) protein of Leptospira interrogans binds extracellular matrix components, plasminogen and 2 integrin. MICROBIOLOGY AND IMMUNOLOGY, v. 60, n. 9, p. 586-598, SEP 2016. Web of Science Citations: 3.
FERNANDES, LUIS G.; SIQUEIRA, GABRIELA H.; TEIXEIRA, ALINE R. F.; SILVA, LUCAS P.; FIGUEREDO, JUPCIANA M.; COSATE, MARIA R.; VIEIRA, MONICA L.; NASCIMENTO, ANA L. T. O. Leptospira spp.: Novel insights into host-pathogen interactions. VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, v. 176, p. 50-57, AUG 2016. Web of Science Citations: 13.
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. Web of Science Citations: 2.
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. Web of Science Citations: 10.
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. Web of Science Citations: 3.
SIQUEIRA, GABRIELA H.; ATZINGEN, MARINA V.; DE SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; NASCIMENTO, ANA L. T. O. Leptospira interrogans Lsa23 protein recruits plasminogen, factor H and C4BP from normal human serum and mediates C3b and C4b degradation. MICROBIOLOGY-SGM, v. 162, n. 2, p. 295-308, FEB 2016. Web of Science Citations: 13.
TEIXEIRA, ALINE F.; DE MORAIS, ZENAIDE M.; KIRCHGATTER, KARIN; ROMERO, ELIETE C.; VASCONCELLOS, SILVIO A.; NASCIMENTO, ANA LUCIA T. O. Features of Two New Proteins with OmpA-Like Domains Identified in the Genome Sequences of Leptospira interrogans. PLoS One, v. 10, n. 4 APR 7 2015. Web of Science Citations: 13.

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