"Evaluation of the immune evasion by pathogenic Leptospira interrogans at the terminal complement system pathway level"

• Grant number: 14/03792-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2014
• End date: July 31, 2015
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Ana Lucia Tabet Oller do Nascimento
• Grantee: Gabriela Hase Siqueira
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Leptospirosis is a worldwide zoonosis disease caused by pathogenic species of the genus Leptospira that affects several species of animals, including humans. This disease is responsible for economic damages to both, human and animal health. Disease control measures towards the control of rodents and improvement of the sanitary conditions of the population are difficult to implement. Vaccination is also a challenge to be overcome because the vaccines available in the market fail to induce a long-lasting and broad-spectrum protection. Understanding the pathogenesis of a microorganism may help to develop strategies against it; regarding leptospires little is known about their mechanisms of invasion and pathogenicity. When invading a host, a microorganism must be able to escape the innate defense mechanisms of the host in order to colonize target tissues. A few years ago it has been observed the ability of pathogenic leptospires to escape and survive the action of the complement system, a key component of the innate immune. More recently it has been shown the binding of leptospires to soluble regulators of this system for modulation of the immune response. One of the survival strategies used by some pathogens, but little explored, is the evasion of the terminal complement system pathway. This project thus aims to evaluate the ability of pathogenic leptospires to inhibit this pathway, as well as, to identify possible proteins involved in this process. The neutralization of these proteins could prevent the colonization of host tissues by these bacteria and can represent an effective strategy for vaccine developing against leptospirosis.

Scientific publications

(5)

(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)

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. (12/23913-9, 14/03792-8)

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)

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. (14/50981-0, 12/23913-9, 14/03792-8)

SIQUEIRA, GABRIELA H.; DE SOUZA, GISELE O.; HEINEMANN, MARCOS B.; VASCONCELLOS, SILVIO A.; NASCIMENTO, ANA L. T. O.. The role of Lsa23 to mediate the interaction of Leptospira interrogans with the terminal complement components pathway. Microbial Pathogenesis, v. 112, p. 182-189, NOV 2017. (14/50981-0, 14/03792-8)

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, p. 14-pg., 2016-02-01. (12/23913-9, 14/03792-8)