Assessment of the role of two proteins of Leptospira interrogans in the pathogenesis and in the immunoprotective activity in animal model

• Grant number: 22/08985-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: December 01, 2022
• End date: November 30, 2026
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ana Lucia Tabet Oller do Nascimento
• Grantee: Igor Rodolpho Matheus Silva
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 19/17488-2 - Advancing the understanding of pathogenesis and virulence of Leptospira interrogans through proteomics, structural, mutagenesis and immunological analyses, AP.TEM

Abstract

Leptospirosis is a worldwide spread zoonosis caused by pathogenic spirochetes of the genus Leptospira. The disease affects humans and animals. In urban centers, rats are the disseminators of leptospirosis as they harbor the bacteria in the kidneys, continuously excreting them alive, contaminating water and soil. In Brazil, the most frequent epidemics occur during the rainy season, a time of flooding that, associated with poor sanitation conditions, favor contact with a contaminated environment. The understanding of the pathogenicity mechanisms of leptospires is essential to block the action of this pathogen. In this sense, the identification of conserved outer membrane proteins are the main research targets, since this surface location facilitates the interaction with the host. In this sense, the project aims to characterize the involvement of 2 Leptospira interrogans surface proteins, LIC11664 and LIC10499, their interactions with endothelial and epithelial cells in culture, as well as with host components. The coding sequences will have their genes cloned and expressed in E. coli strains. The recombinant proteins will be purified by metal affinity chromatography and analyzed for their structure by the circular dichroism technique. BALB/c animals will be immunized with the recombinant proteins for the production of polyclonal antiserum and the sera obtained will be used in several experiments to probe the presence of these proteins. These, in their recombinant form, will be evaluated for reactivity to components of the host, such as extracellular matrix and plasma, such as plasminogen and fibrinogen, and components of the complement system. The proteins will be analyzed for interactions with endothelial and epithelial cells in culture and for immunoprotective activities in an animal model. These activities will be validated by obtaining mutants of saprophytic and pathogenic leptospires. These results will characterize these proteins for their role in the pathogenicity of leptospires and for their potential for vaccine development. (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)

SILVA, IGOR R. M.; TAKAHASHI, MARIA B.; TEIXEIRA, ALINE F.; NASCIMENTO, ANA L. T. O.. Evaluation of binding activities of a putative lipoprotein LIC_13355 of Leptospira spp.. FEBS OPEN BIO, v. N/A, p. 15-pg., 2024-12-12. (19/17488-2, 22/08985-5, 17/26223-7, 16/11541-0, 19/05466-4)