Study of Type II secretion system and the molecular bases involved c-di-GMP signaling on Leptospira interrogans Serovar Copenhageni

Abstract

I am starting my activities as a lecturer in the Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo. During my scientific carrier, I have been working with different class of proteins, such as conserved hypothetical proteins and proteins involved in type IV pili biogenesis, from Xanthomonas axonopodis pv citri, a plant pathogen, in the laboratory of Professor Dr. Shaker Chuck Farah, IQ-USP. The goal of the project that I am requesting, is the structural and function studies of several proteins involved in the synthesis, degradation, binding to bacterial second messenger c-di-GMP from Leptospira interrogans Copenhageni pathogen. Besides the study of proteins involved in c-di-GMP signaling, we aim to study the functional and structural proteins present in the gene cluster of single secretion system found in the genome of Leptospira interrogans Copenhageni, the type II secretion system. The choice of Leptospira interrogans copenhageni strain was based on the relevance of this pathogen to the Brazilian and public health world. Leptospira interrogans is the causative agent of leptospirosis, an infectious disease re-emerging zoonosis that affects various animals including humans. More than 500 thousand cases of severe leptospirosis are reported each year, 5 to 15% of leptospirosis cases the clinical conditions may progress to severe conditions, known as Weil syndrome. In this cases, the patients could have jaundice, real failure, meningitis, hypotension, and 10% of patients died. The diagnosis is very difficult to have a symptoms very similar to other diseases. In severe cases of leptospirosis, hospitalization of the patient is required for kidney dialysis, hemorrhagic treatment and intensive medical monitoring. Thus, leptospirosis treatment is costly and represents an economic problem for the public health system. We intend to contribute to the spirochetes molecular biology understanding and contribute to the elucidation of the virulence pathways. (AU)