Renal pathological aspects related to persistence and chronic infection by Leptospira interrogans

• Grant number: 21/01122-9
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2021
• End date: June 30, 2023
• 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

Bacteria of the genus Leptospira are spirochetes equipped with efficient strategies for dissemination in the host. Pathogenic species belonging to this genus cause leptospirosis, which can manifest as an acute, chronic or asymptomatic illness, mainly in reservoir hosts, such as mice and rats. About 10 to 20% of cases in humans can evolve to severe forms, leading to shock and death. In this project, divided into two parts, we aim to investigate aspects related to the persistence of leptospires in the host's kidneys. In subproject 1, our goal is to evaluate the influence of the stimulation by the Hepatocyte Growth Factor (HGF) in the cellular communication pathways, and to establish whether the supplementary administration of this growth factor could become a therapeutic strategy for the preventive treatment of renal fibrosis caused by infection with L. interrogans. In subproject 2, we aim to evaluate whether the L1-130 strain, belonging to a pathogenic, virulent species, regularly maintained in the laboratory as a study model, is able to subvert the action of the alternative pathway of the complement system, inactivating molecules in the cascade produced locally by kidney cells. Our hypothesis is that such a mechanism may contribute to the survival of these bacteria in the host kidneys. The characterization of mechanisms related to the pathogenesis of Leptospira bacteria has been our main line of research. Unraveling the mechanisms underlying the persistence of these spirochetes in the kidneys will help us to better understand the reasons why these organs are considered immunoprivileged sites in leptospirosis. (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)

PRADO, LUAN GAVIAO; BARBOSA, ANGELA SILVA. Understanding the Renal Fibrotic Process in Leptospirosis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 19, OCT 2021. (21/01122-9)