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Understanding the c-di-GMP signaling networks and the Type II secretion system present into the human pathogen Leptospira interrogans Copenhageni

Abstract

The goals of the project are the study of proteins of the human pathogen Leptospira interrogans. This bacterium is the causative agent of leptospirosis, a re-emerging infectious disease considered a zoonosis worldwide that affects several animals including humans. More than 500,000 cases of severe leptospirosis are reported per year, and in severe cases the patient ends up dying. Due to the medical importance of this pathogen functional and structural studies of the c-di-GMP signalling pathways and the type II secretion system will contribute to the understanding of the molecular bases involved in the biology of this spirochete and may contribute to the elucidation of its virulence pathways. Possible results from our research may result in the creation of drugs to combat leptospirosis infection. However, this is not the goal of this project. The project proposed here has two main objectives: 1- Structural and functional study of proteins involved in the synthesis, degradation, binding to the second bacterial messenger, c-di-GMP and 2- structural and functional study of the Leptospira type II secretion system, the only secretory system noted in its genome.Our studies will be done using different techniques of structural biology such as X-ray diffraction and cryo-electron microscopy, as well as several techniques of biochemistry of macromolecules, such as Western Blotting, kinetic enzymatic, among others. In general, this proposal encompasses well established techniques in our research group and innovative techniques such as cryo-electron microscopy. The results obtained in this project will contribute to the scientific community with the projection of publications in journals of high scientific impact. (AU)

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Scientific publications (4)
(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)
MACHADO, RAFAEL R. G.; GLASER, TALITA; ARAUJO, DANIELLE B.; PETIZ, LYVIA LINTZMAIER; OLIVEIRA, DANIELLE B. L.; DURIGON, GIULIANA S.; LEAL, ALESSANDRA L.; PINHO, JOAO RENATO R.; FERREIRA, LUIS C. S.; ULRICH, HENNING; DURIGON, EDISON L.; GUZZO, CRISTIANE RODRIGUES. Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 Replication by Hypertonic Saline Solution in Lung and Kidney Epithelial Cells. ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE, v. 4, n. 5, p. 1514-1527, OCT 8 2021. Web of Science Citations: 0.
DE SOUZA, ANACLETO SILVA; DE SOUZA, ROBSON FRANCISCO; GUZZO, CRISTIANE RODRIGUES. Quantitative structure-activity relationships, molecular docking and molecular dynamics simulations reveal drug repurposing candidates as potent SARS-CoV-2 main protease inhibitors. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, JUL 2021. Web of Science Citations: 0.
SIBINELLI-SOUSA, STEPHANIE; HESPANHOL, JULIA T.; NICASTRO, GIANLUCCA G.; MATSUYAMA, BRUNO Y.; MESNAGE, STEPHANE; PATEL, ANKUR; DE SOUZA, ROBSON F.; GUZZO, CRISTIANE R.; BAYER-SANTOS, ETHEL. A Family of T6SS Antibacterial Effectors Related to L,D-Transpeptidases Targets the Peptidoglycan. CELL REPORTS, v. 31, n. 12 JUN 23 2020. Web of Science Citations: 0.
ALINE DIAS DA, PURIFICACAO; NATHALIA MARINS DE, AZEVEDO; GABRIEL GUARANY DE, ARAUJO; ROBSON FRANCISCO DE, SOUZA; RODRIGUES, GUZZO CRISTIANE. The World of Cyclic Dinucleotides in Bacterial Behavior. Molecules, v. 25, n. 10 MAY 2020. Web of Science Citations: 0.

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