Colonization and evasion of host complement system by Leptospira: I. Functional characterization of the Elongation Factor Tu (EF-Tu) II. Interaction with human vitronectin

• Grant number: 11/07297-3
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2011
• End date: June 30, 2013
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Angela Silva Barbosa
• Grantee: Angela Silva Barbosa
• Host Institution: Instituto Butantan. São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Danielly Gonçalves Wolff ; Lourdes Isaac ; Patricia Antonia Estima Abreu de Aniz ; Silvio Arruda Vasconcellos

Abstract

Leptospirosis is a zoonosis caused by pathogenic bacteria from the genus Leptospira. The disease represents a serious public health problem in underdeveloped tropical countries. More than 500,000 cases of severe leptospirosis are reported each year, with mortality rates exceeding 10% (World Health Organization, 1999). Rodents are the main urban reservoir of the disease, shedding viable leptospires throughout their lives in the environment. Leptospires infect hosts through small abrasions in the skin or mucous membranes and they rapidly disseminate to target organs. Over the past few years, our group has focused on the identification of immune evasion mechanisms presented by pathogenic leptospires. In this context, functional characterization of leptospiral outer membrane proteins, which represent the main targets for interaction with host molecules, is of great relevance. This research project is divided in two parts: 1) functional characterization of the leptospiral Elongation Factor Tu (EF-Tu) with regard to its interaction with human complement regulators, extracellular matrix components, and coagulation cascade molecules; 2) evaluation of the interaction of vitronectin - a glycoprotein found in the extracellular matrix and in the plasma, playing a crucial role in cell migration, tissue repair and regulation of the terminal pathway of complement activation - with pathogenic leptospires as a mechanism of immune evasion. The identification of mechanisms adopted by this bacterium to subvert the immune system, and the characterization of proteins that interact with host molecules may contribute to the development of therapeutic strategies to fight the disease. (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 BEZERRA; MIRAGAIA, LIDIA DOS SANTOS; DANTAS BREDA, LEANDRO CARVALHO; ABE, CECILIA MARI; BRAGA SCHMIDT, MARIANA COSTA; MORO, ANA MARIA; MONARIS, DENIZE; CONDE, JONAS NASCIMENTO; JOZSI, MIHALY; ISAAC, LOURDES; et al. Pathogenic Leptospira Species Acquire Factor H and Vitronectin via the Surface Protein LcpA. Infection and Immunity, v. 83, n. 3, p. 888-897, MAR 2015. (11/07297-3, 10/50043-0)

SALAZAR, NATALIA; CASTIBLANCO-VALENCIA, MONICA MARCELA; DA SILVA, LUDMILA BEZERRA; DE CASTRO, IRIS ARANTES; MONARIS, DENIZE; MASUDA, HANA PAULA; BARBOSA, ANGELA SILVA; MATTOS AREAS, ANA PAULA. Staphylococcus aureus Manganese Transport Protein C (MntC) Is an Extracellular Matrix- and Plasminogen-Binding Protein. PLoS One, v. 9, n. 11, NOV 19 2014. (11/07297-3, 10/50043-0)

WOLFF, DANIELLY G.; CASTIBLANCO-VALENCIA, MONICA M.; ABE, CECILIA M.; MONARIS, DENIZE; MORAIS, ZENAIDE M.; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; ISAAC, LOURDES; ABREU, PATRICIA A. E.; BARBOSA, ANGELA S.. Interaction of Leptospira Elongation Factor Tu with Plasminogen and Complement Factor H: A Metabolic Leptospiral Protein with Moonlighting Activities. PLoS One, v. 8, n. 11, NOV 27 2013. (11/07297-3, 10/50043-0)