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

• Grant number: 19/00195-2
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2019
• End date: July 31, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Cristiane Rodrigues Guzzo Carvalho
• Grantee: Cristiane Rodrigues Guzzo Carvalho
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 20/14914-8 - Characterization of LIC_11920 and its role in c-di-GMP signaling, BP.TT; 19/18356-2 - Expression and purification of the GspC-GspD complex of the type II secretion system of Leptospira interrogans Copenhgeni, BP.TT

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)

Scientific publications

(9)

(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)

DE SOUZA, ANACLETO SILVA; DE FREITAS AMORIM, VITOR MARTINS; DE SOUZA, ROBSON FRANCISCO; GUZZO, CRISTIANE RODRIGUES. Molecular dynamics simulations of the spike trimeric ectodomain of the SARS-CoV-2 Omicron variant: structural relationships with infectivity, evasion to immune system and transmissibility. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, v. N/A, p. 18-pg., 2022-10-29. (20/04680-0, 21/00070-5, 19/00195-2, 16/09047-8)

DE SOUZA, ANACLETO SILVA; DE FREITAS AMORIM, VITOR MARTINS; GUARDIA, GABRIELA D. A.; DOS SANTOS, FILIPE F.; ULRICH, HENNING; GALANTE, PEDRO A. F.; DE SOUZA, ROBSON FRANCISCO; GUZZO, CRISTIANE RODRIGUES. Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern: A Perspective for Emerging More Transmissible and Vaccine-Resistant Strains. Viruses-Basel, v. 14, n. 4, p. 21-pg., 2022-04-01. (18/07366-4, 20/06091-1, 19/00195-2, 16/09047-8, 20/14158-9, 20/04680-0, 17/18246-7, 17/19541-2, 18/15579-8)

VENTURA FERNANDES, BIANCA H.; FEITOSA, NATALIA MARTINS; BARBOSA, ANA PAULA; BOMFIM, CAMILA GASQUE; GARNIQUE, ANALI M. B.; ROSA, IVANA F.; RODRIGUES, MAIRA S.; DORETTO, LUCAS B.; COSTA, DANIEL F.; CAMARGO-DOS-SANTOS, BRUNO; et al. oxicity of spike fragments SARS-CoV-2 S protein for zebrafish: A tool to study its hazardous for human health. Science of The Total Environment, v. 813, MAR 20 2022. (19/00195-2, 18/07098-0, 20/05761-3, 17/17303-7, 20/04680-0, 14/04294-1, 19/21739-0, 19/19939-1, 19/18356-2, 19/14285-3, 19/12234-2)

DE SOUZA, ANACLETO SILVA; AMORIM, VITOR MARTINS DE FREITAS; GUARDIA, GABRIELA D. A.; DOS SANTOS, FELIPE R. C.; DOS SANTOS, FILIPE F.; DE SOUZA, ROBSON FRANCISCO; JUVENAL, GUILHERME DE ARAUJO; HUANG, YIHUA; GE, PINGJU; JIANG, YINAN; et al. Molecular Dynamics Analysis of Fast-Spreading Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Their Effects on the Interaction with Human Angiotensin-Converting Enzyme 2. ACS OMEGA, v. 7, n. 35, p. 10-pg., 2022-08-24. (20/06091-1, 17/18246-7, 17/19541-2, 20/04680-0, 19/00195-2, 16/09047-8, 18/15579-8, 18/07366-4, 20/14158-9)

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. (20/04680-0, 19/00195-2, 16/09047-8)

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. (18/04553-8, 17/02178-2, 16/09047-8, 19/00195-2, 17/17303-7, 18/25316-4, 16/00458-5, 18/13819-1)

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, v. 40, n. 21, p. 18-pg., 2022-01-01. (19/00195-2, 16/09047-8, 20/04680-0)

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. (18/21076-9, 16/08414-7, 17/10611-8, 18/08996-1, 19/00195-2)

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; et al. 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. (20/06409-1, 19/00195-2, 18/07366-4, 17/24769-2, 16/20045-7, 20/04680-0)