Leptospira-host interaction: identification and characterization of a bacterial ligand for human complement regulators FH and C4BP

• Grant number: 09/01778-0
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2009
• End date: May 31, 2011
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Angela Silva Barbosa
• Grantee: Angela Silva Barbosa
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Leptospirosis is a spirochetal disease caused by pathogenic members of the genus Leptospira. After penetrating the host, leptospires have the ability to disseminate and to trigger a specific immune response. Their capacity to adhere to host cells and to escape the host´s innate immune defense systems contibutes to colonization and persistence of those pathogens in the organism. A number of pathogenic microorganisms have evolved strategies to circumvent the immune defense systems of a variety of hosts, notably mechanisms to escape complement activation and / or lytic complement attack. Recently, we have shown that pathogenic leptospiral strains are able to bind C4b Binding Protein (C4BP). Surface-bound C4BP retained its cofactor activity, indicating that acquisition of this complement regulator may contribute to leptospiral serum resistance. The ability of six leptospiral proteins to interact with Factor H (FH) and C4BP was also evaluated. One of them interacted with both complement regulators. The aims of this project are: to extend previous results concerning the interaction of the above-mentioned protein with FH and C4BP; to perform further characterization regarding expression and degree of conservation of the protein among pathogenic and non-pathogenic leptospiral species; to confirm the subcellular localization and to evaluate its vaccine potential in an animal model. (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)

BARBOSA, ANGELA S.; MONARIS, DENIZE; SILVA, LUDMILA B.; MORAIS, ZENAIDE M.; VASCONCELLOS, SILVIO A.; CIANCIARULLO, AURORA M.; ISAAC, LOURDES; ABREU, PATRICIA A. E.. Functional Characterization of LcpA, a Surface-Exposed Protein of Leptospira spp. That Binds the Human Complement Regulator C4BP. Infection and Immunity, v. 78, n. 7, p. 3207-3216, JUL 2010. (09/01778-0)