IDENTIFICATION OF NOVEL VIRULENCE FACTORS OF LEPTOSPIRA INVOLVED IN ADHESION, INVASION AND SERUM RESISTANCE

• Grant number: 16/05878-2
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2016
• End date: August 31, 2018
• 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

Spirochetes of the genus Leptospira may cause leptospirosis, a zoonosis of worldwide distribution. The Leptospira genus includes pathogenic and saprophytic species, which are classified into more than 300 serovars. Pathogenic leptospires have evolved virulence strategies to successfully colonize a variety of hosts, but the mechanisms of disease pathogenesis in leptospirosis are still poorly defined. A small number of virulence factors has been identified so far through the recent development of genetic tools that allowed assessment of a few mutants in animal models. Binding to host molecules certainly contributes to colonization, invasion and immune evasion. While progress has been made in this field, there remains a lack of understanding of how Leptospira causes disease. The main goal of this project, subdivided in two parts, is to identify surface proteins of Leptospira that contribute to host colonization. In previous studies by our group, outer membrane proteins were incubated with purified host proteins (extracellular matrix and coagulation cascade components as well as negative complement regulators) pre-immobilized on magnetic beads. The ligands were identified by mass spectrometry. Five proteins containing adhesion-related domains, present only in pathogenic species of Leptospira, were selected for further characterization. In subproject 1, the identified proteins will be produced in Escherichia coli and a number of functional assays will be performed to better characterize the interactions observed. In subproject 2, the involvement of two moonlighting proteins - enolase and GAPDH - in Leptospira pathogenesis will be evaluated. Interest on investigating and exploring the role of moonlighting proteins as virulence factors in spirochetes arose quite recently and our group is recognized as a pioneer in this particular subject. In the present project we aim to characterize the functional consequences of plasminogen binding to Leptospira enolase and also evaluate whether leptospiral GAPDH displays moonlighting activities related to adhesion, invasion and / or immune evasion. Given the need to develop preventive strategies that can interfere with the invasion and immune evasion mechanisms of this bacterium, the identification and characterization of proteins that may be involved in these processes is of fundamental importance. (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)

ABREU, AFONSO G.; BARBOSA, ANGELA S.. How Escherichia coli Circumvent Complement-Mediated Killing. FRONTIERS IN IMMUNOLOGY, v. 8, APR 20 2017. (16/05878-2)

SALAZAR, NATALIA; YAMAMOTO, BRUNO BERNARDI; LIMA DE SOUZA, MATILDE COSTA; DA SILVA, LUDMILA BEZERRA; MATTOS AREAS, ANA PAULA; BARBOSA, ANGELA SILVA. The C-Terminal Domain of Staphylococcus aureus Zinc Transport Protein AdcA Binds Plasminogen and Factor H In Vitro. PATHOGENS, v. 11, n. 2, p. 15-pg., 2022-02-01. (16/05878-2)