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Structural characterization of surface proteins of Leptospira interrogans - A view of pathogen-host interactions

Grant number: 18/20321-0
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): December 17, 2018
Effective date (End): August 31, 2019
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Ana Lucia Tabet Oller Do Nascimento
Grantee:Jademilson Celestino dos Santos
Supervisor abroad: Partho Ghosh
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Local de pesquisa : University of California, San Diego (UC San Diego), United States  
Associated to the scholarship:17/25167-6 - Structural characterization of surface proteins of Leptospira interrogans and thermodynamics of the interaction with host-components, BP.PD

Abstract

Leptospirosis is a worldwide zoonotic infection with a high prevalence in tropical and subtropical regions, and has been identified as an emerging infectious diseases. Each year more than 1 million cases of leptospirosis are reported in humans with approximately 60,000 annual deaths. Pathogenic species of Leptospira cause the disease by colonizing the kidneys of wild and domestic animals. Humans are contaminated through contact with these bacteria via the urine of infected animals - primarily rats in urban areas. The molecular aspects related to Leptospira virulence and pathogenesis are still poorly understood. This lack of molecular information has limited the development of efficient vaccines or diagnostics. Our group has investigated the genome sequences of L. interrogans surface-exposed proteins because, because such proteins are capable of interacting with host components and participating in the establishment of an infection. An important interaction occurs between the surface-exposed protein Lsa33 with the coagulation cascade component fibrinogen (Fg), resulting in decrease in fibrin clotting and thus favoring bacterial dissemination. The goal of this proposal is to reveal a possible mechanism of pathogenesis of L. interrogans. For this, we intend to use biochemical and biophysical approaches to determine the structures of free Lsa33 and the Lsa33-Fg complex. The group of Prof. Partho Ghosh at UCSD has expertise in the use of structural biology in understanding how proteins produced by microbial pathogens interact with host macromolecules, including prominently Fg, and how these interactions lead to infectious disease. This expertise will be beneficial in the intersection of the structural biology with host-pathogen interactions.