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Identification of Leptospira proteases involved in the degradation of extracellular matrix proteins

Grant number: 13/17419-4
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2013
Effective date (End): September 30, 2017
Field of knowledge:Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
Principal Investigator:Angela Silva Barbosa
Grantee:Ludmila Bezerra da Silva
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Leptospirosis, a zoonosis widely spread around the world, is caused by spirochetes of the genus Leptospira. Highly frequent in tropical and subtropical areas, the disease represents an important public health problem. In the last years, researches have been focused on factors related to the pathogenesis of the disease. Pathogenic leptospires have the ability to circumvent host´s defense mechanisms by avoiding complement mediated lysis. Moreover, they express membrane proteins that interact with cells and extracellular matrix proteins from the host. The aim of this project is to evaluate the secretion of proteases by different Leptospira species capable of directly degrading extracellular matrix proteins. Previous assays performed by our group have demonstrated that proteins secreted by pathogenic leptospires are able to cleave and inactivate key molecules of the complement system. The ability to cleave conjunctive tissue molecules may certainly contribute to invasion and tissue destruction observed upon infection with these bacteria. Among the proteases secreted by pathogenic leptospires, we selected the metalloprotease NprT from the thermolysin family to perform proteolytic activity assays. This protease shares a high degree of similarity with proteins present in other pathogens, known to degrade extracellular matrix components, thus representing a relevant candidate for substrates such as laminin, fibronectin, collagens, elastin and fibrinogen. The identification and characterization of proteases capable of cleaving extracellular matrix proteins is of great relevance and may contribute to the development of therapeutic strategies to fight the disease.

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Scientific publications
(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)
DA SILVA, LUDMILA B.; MENEZES, MILENE C.; KITANO, EDUARDO S.; OLIVEIRA, ANA K.; ABREU, AFONSO G.; SOUZA, GISELE O.; HEINEMANN, MARCOS B.; ISAAC, LOURDES; FRAGA, TATIANA R.; SERRANO, SOLANGE M. T.; et al. Leptospira interrogans Secreted Proteases Degrade Extracellular Matrix and Plasma Proteins From the Host. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 8, . (13/17419-4, 14/00926-3)
MORAES, CLAUDIA T. P.; LONGO, JONATHAN; SILVA, LUDMILA B.; PIMENTA, DANIEL C.; CARVALHO, ENEAS; MORONE, MARIANA S. L. C.; DA ROS, NANCY; SERRANO, SOLANGE M. T.; SANTOS, ANA CAROLINA M.; PIAZZA, ROXANE M. F.; et al. Surface Protein Dispersin of EnteroaggregativeEscherichia coliBinds Plasminogen That Is Converted Into Active Plasmin. FRONTIERS IN MICROBIOLOGY, v. 11, . (18/06610-9, 16/18583-0, 13/17419-4)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVA, Ludmila Bezerra da. Identification of Leptospira proteases involved in the degradation of extracellular matrix and plasma proteins. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD) São Paulo.

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