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Leptospira-host interaction: aspects related to tissue invasion and innate immune system evasion

Grant number: 14/00926-3
Support type:Regular Research Grants
Duration: June 01, 2014 - May 31, 2016
Field of knowledge:Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
Principal Investigator:Angela Silva Barbosa
Grantee:Angela Silva Barbosa
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


Leptospirosis, caused by spirochetes of the genus Leptospira, is a zoonosis of worldwide distribution. Highly frequent in tropical and subtropical areas, the disease represents an important public health problem. Pathogenic leptospires have the ability to escape the natural defense mechanisms of the body by circumventing complement mediated lysis. They also express a number of membrane proteins capable of interacting with extracellular matrix molecules and host cells. Moreover, leptospires acquire human plasminogen to their surfaces, which is converted to its active form, plasmin. Recent data by our group indicate that proteins secreted by Leptospira pathogenic species cleave several human complement proteins, rendering them inactive. Our group research is focused on the identification of invasion mechanisms as well as of immune evasion strategies employed by pathogenic leptospires. The main goals of this project are: identification of Leptospira proteases involved in the degradation of extracellular matrix and coagulation cascade molecules (subproject # 1) and evaluation of the relevance of the interaction of vitronectin with leptospiral outer membrane proteins (subproject # 2). The identification and the characterization of proteases that degrade ECM molecules and of bacterial surface proteins involved in the interaction with negative complement regulators is of great relevance, contributing to the development of therapeutic and/or preventive strategies that may interfere with invasion and tissue destruction observed in leptospirosis as well as in the immune evasion mechanism presented by this pathogen. (AU)

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.; BARBOSA, ANGELA S. Leptospira interrogans Secreted Proteases Degrade Extracellular Matrix and Plasma Proteins From the Host. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 8, MAR 27 2018. Web of Science Citations: 1.
SALAZAR, NATALIA; LIMA DE SOUZA, MATILDE COSTA; BIASIOLI, AMANDA GAMEIRO; DA SILVA, LUDMILA BEZERRA; BARBOSA, ANGELA SILVA. The multifaceted roles of Leptospira enolase. Research in Microbiology, v. 168, n. 2, p. 157-164, FEB-MAR 2017. Web of Science Citations: 7.
FRAGA, TATIANA RODRIGUES; ISAAC, LOURDES; BARBOSA, ANGELA SILVA. Complement Evasion by Pathogenic Leptospira. FRONTIERS IN IMMUNOLOGY, v. 7, DEC 21 2016. Web of Science Citations: 9.

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