Identification of leptospiral proteases involved with scape mechanisms from the human complement system.

• Grant number: 09/11714-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2010
• End date: August 31, 2013
• Field of knowledge: Biological Sciences - Immunology - Immunochemistry
• Principal Investigator: Lourdes Isaac
• Grantee: Tatiana Rodrigues Fraga
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Leptospirosis is a worldwide zoonosis. The disease represents a serious health problem in urban areas with large populations of rodents, the main reservoirs of leptospires. After invasion, pathogenic leptospires rapidly disseminates through the tissues and stimulates a specific immune response. Adhesion and ability of escaping the host natural defense mechanisms are followed by colonization and persistence of the bacteria in the organism. Several pathogenic microorganisms, especially those that reach the blood circulation, developed multiple evasion strategies to escape the host immune system, including activation and/or attack mediated by the complement system. Recently, it was demonstrated that only pathogenic leptospires are able to bind human Factor H (FH) and C4b Binding Protein (C4BP), two plasmatic regulators from the complement system. The acquisition of these negative regulators may contribute to the serum resistance of the pathogenic bacteria. New data from our research group indicates that these bacteria could have other evasion mechanisms from human complement. Preliminary experiments showed that the inactivation of C3b, a key molecule from the complement system, also happens without FH and FI, suggesting that pathogenic leptospires should express proteases that promote the fragmentation of C3b. The aim of this project is to investigate the leptospiral evasion mechanisms from the human complement system, particularly the fragmentation of C3b, C4b and C5 by membrane and/or secreted proteases. The identification and characterization of proteases that inactivates molecules from the innate immune system is extremely important, since it could contribute to the development of new therapeutic and preventive strategies, interfering with leptospira evasion mechanisms from the immune system.

Academic Publications

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

FRAGA, Tatiana Rodrigues. Identification of leptospiral proteases involved in immune evasion mechanisms from the human complement system.. 2014. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.