Search for surface proteins among the genome sequences of Leptospira interrogans: functional and immunological characterization to understanding mechanisms involved in the bacterial pathogenesis

• Grant number: 14/50981-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: November 01, 2015
• End date: November 30, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Ana Lucia Tabet Oller do Nascimento
• Grantee: Ana Lucia Tabet Oller do Nascimento
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated scholarship(s): 18/06201-1 - Identification of virulence factors of Leptospira interrogans through comparative proteomics analysis, BP.DR; 18/08131-0 - Heterologous expression of the gene LIC13259 in the saprophyte Leptospira biflexa and their acquisition capacity to evade the human immune system, BP.DR; 18/21959-8 - Evaluation of the functional role of HtrA-like proteins present in pathogenic strains by creating mutants of Leptospira biflexa and Leptospira interrogans, BP.DD; + associated scholarships 18/09652-4 - Evaluation of the interaction of Leptospira interrogans proteins with host components by constructing recombinant Leptospira biflexa, BP.DR; 17/26223-7 - Evaluation of functional role of Leptospira interrogans surface proteins as endothelial and epithelial cells receptors of the host, BP.DD; 17/25167-6 - Structural characterization of surface proteins of Leptospira interrogans and thermodynamics of the interaction with host-components, BP.PD; 17/01411-5 - Cloning, expression and characterization of HtrA proteins of Leptospira interrogans, BP.MS; 17/01102-2 - Biochemical and immunological evaluation of hypothetical surface proteins of Leptospira interrogans, BP.DD; 16/04295-3 - Interaction of two Leptospira interrogans proteins to plasma and extracellular matrix components of the host, BP.MS; 16/01384-5 - Evaluation of the functional role of two Leptospira interrogans proteins in the adhesion process of the pathogen to the host, BP.MS - associated scholarships

Abstract

Leptospirosis is a global wide spread zoonosis caused by pathogenic spirochetes of the genus Leptospira. There is no effective vaccine. The Identification of surface proteins among pathogenic strains is the research focus to elucidated mechanisms involved (AU)

Scientific publications

(34)

(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)

TEIXEIRA, ALINE F.; FERNANDES, LUIS G. V.; SOUZA FILHO, ANTONIO; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; NASCIMENTO, ANA L. T. O.. Evaluation of Lsa46 and Lsa77 Leptospiral Proteins for Their Immunoprotective Activities in Hamster Model of Leptospirosis. BIOMED RESEARCH INTERNATIONAL, 2018. (16/11541-0, 14/50981-0, 17/06731-8)

SANTOS, JADSON V.; PEREIRA, PRISCILA R. M.; FERNANDES, LUIS G. V.; SIQUEIRA, GABRIELA HASE; DE SOUZA, GISELE O.; SOUZA FILHO, ANTONIO; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; CHAPOLA, ERICA G. B.; NASCIMENTO, ANA L. T. O.. Binding of human plasminogen by the lipoprotein LipL46 of Leptospira interrogans. MOLECULAR AND CELLULAR PROBES, v. 37, p. 12-21, FEB 2018. (12/24164-0, 14/50981-0, 15/02590-5)

NASCIMENTO FILHO, EDSON G.; VIEIRA, MONICA L.; TEIXEIR, ALINE F.; SANTOS, JADEMILSON C.; FERNANDES, LUIS G. V.; PASSALIA, FELIPE J.; DAROZ, BRENDA B.; ROSSINI, AMANDA; KOCHI, LEANDRO T.; CAVENAGUE, MARIA F.; et al. Proteomics as a tool to understand Leptospira physiology and virulence: Recent advances, challenges and clinical implications. JOURNAL OF PROTEOMICS, v. 180, n. SI, p. 80-87, MAY 30 2018. (17/01411-5, 17/06731-8, 14/50981-0, 17/01102-2, 16/11541-0, 16/04295-3, 16/01384-5)

KOCHI, LEANDRO TOSHIO; FERNANDES, LUIS GUILHERME VIRGILIO; NASCIMENTO, ANA LUCIA TABET OLLER. Heterologous Expression of the Pathogen-Specific LIC11711 Gene in the Saprophyte L. biflexa Increases Bacterial Binding to Laminin and Plasminogen. PATHOGENS, v. 9, n. 8, AUG 2020. (18/09652-4, 17/06731-8, 14/50981-0)

TEIXEIRA, ALINE F.; FERNANDES, V, LUIS G.; CAVENAGUE, MARIA F.; TAKAHASHI, MARIA B.; SANTOS, JADEMILSON C.; PASSALIA, FELIPE J.; DAROZ, BRENDA B.; KOCHI, LEANDRO T.; VIEIRA, MONICA L.; NASCIMENTO, ANA L. T. O.. Adjuvanted leptospiral vaccines: Challenges and future development of new leptospirosis vaccines. Vaccine, v. 37, n. 30, p. 3961-3973, JUL 9 2019. (17/01411-5, 17/06731-8, 17/25167-6, 14/50981-0, 17/01102-2, 16/11541-0, 17/26223-7, 17/00236-5, 16/01384-5)

VIEIRA, MONICA L.; HERWALD, HEIKO; NASCIMENTO, ANA LUCIA T. O.. The interplay between host haemostatic systems and Leptospira spp. infections. CRITICAL REVIEWS IN MICROBIOLOGY, v. 46, n. 2, MAR 2020. (17/00236-5, 14/50981-0)

GRABARZ, FELIPE; LOPES, ALEXANDRE PAULO YAGUE; BARBOSA, FLAVIA FERREIRA; BARAZZONE, GIOVANA CAPPIO; SANTOS, JADEMILSON CELESTINO; BOTOSSO, VIVIANE FONGARO; JORGE, SORAIA ATTIE CALIL; NASCIMENTO, ANA LUCIA TABET OLLER; ASTRAY, RENATO MANCINI; GONCALVES, VIVIANE MAIMONI. Strategies for the Production of Soluble Interferon-Alpha Consensus and Potential Application in Arboviruses and SARS-CoV-2. LIFE-BASEL, v. 11, n. 6, JUN 2021. (14/50981-0, 16/50413-8)

PEREIRA, PRISCILA R. M.; FERNANDES, LUIS G. V.; DE SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; ROMERO, ELIETE C.; NASCIMENTO, ANA L. T. O.. Multifunctional and Redundant Roles of Leptospira interrogans Proteins in Bacterial-Adhesion and fibrin clotting inhibition. INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, v. 307, n. 6, p. 297-310, SEP 2017. (15/02590-5, 14/50981-0, 12/23913-9, 12/24164-0)

SILVA, LUCAS P.; FERNANDES, LUIS G. V.; VIEIRA, MONICA L.; DE SOUZA, GISELE O.; HEINEMANN, MARCOS B.; VASCONCELLOS, SILVIO A.; ROMERO, ELIETE C.; NASCIMENTO, ANA L. T. O.. Evaluation of two novel leptospiral proteins for their interaction with human host components. PATHOGENS AND DISEASE, v. 74, n. 5, JUL 2016. (14/50981-0, 14/18337-4, 12/23913-9, 12/24164-0)

COSATE, MARIA RAQUEL; SIQUEIRA, GABRIELA HASE; DE SOUZA, GISELE OLIVEIRA; VASCONCELLOS, SILVIO ARRUDA; NASCIMENTO, ANA LUCIA T. O.. Mammalian cell entry (Mce) protein of Leptospira interrogans binds extracellular matrix components, plasminogen and 2 integrin. MICROBIOLOGY AND IMMUNOLOGY, v. 60, n. 9, p. 586-598, SEP 2016. (14/50981-0, 12/23913-9, 14/03792-8)

VIEIRA, MONICA L.; TEIXEIRA, ALINE F.; PIDDE, GISELLE; CHING, ANA T. C.; TAMBOURGI, DENISE V.; NASCIMENTO, ANA LUCIA T. O.; HERWALD, HEIKO. Leptospira interrogans outer membrane protein LipL21 is a potent inhibitor of neutrophil myeloperoxidase. VIRULENCE, v. 9, n. 1, p. 414-425, 2018. (14/50981-0, 14/18337-4)

LOPES, ALEXANDRE P. Y.; AZEVEDO, BRUNA O. P.; EMIDIO, REBECA C.; DAMIANO, DEBORAH K.; NASCIMENTO, ANA L. T. O.; BARAZZONE, GIOVANA C.. In Silico Analysis of Genetic VapC Profiles from the Toxin-Antitoxin Type II VapBC Modules among Pathogenic, Intermediate, and Non-Pathogenic Leptospira. MICROORGANISMS, v. 7, n. 2, FEB 2019. (14/50981-0)

FERNANDES, L. G. V.; HORNSBY, R. L.; NASCIMENTO, A. L. T. O.; NALLY, J. E.. Genetic manipulation of pathogenic Leptospira: CRISPR interference (CRISPRi)-mediated gene silencing and rapid mutant recovery at 37 degrees C. SCIENTIFIC REPORTS, v. 11, n. 1, JAN 19 2021. (14/50981-0, 17/06731-8, 19/20302-8)

PASSALIA, FELIPE JOSE; CARVALHO, ENEAS; HEINEMANN, MARCOS BRYAN; VIEIRA, MONICA LARUCCI; NASCIMENTO, ANA LUCIA T. O.. The Leptospira interrogans LIC10774 is a multifunctional surface protein that binds calcium and interacts with host components. MICROBIOLOGICAL RESEARCH, v. 235, MAY 2020. (17/00236-5, 14/50981-0, 17/01102-2, 18/07054-2)

SANTOS, JADEMILSON C.; VIEIRA, MONICA L.; ABENDROTH, JAN; LIN, TAO; STAKER, BART L.; MYLER, PETER J.; NASCIMENTO, ANA LUCIA T. O.. Structural analysis of CACHE domain of the McpA chemoreceptor from Leptospira interrogans. Biochemical and Biophysical Research Communications, v. 533, n. 4, p. 1323-1329, DEC 17 2020. (17/25167-6, 14/50981-0)

DAROZ, BRENDA BEVILAQUA; VIRGILIO FERNANDES, LUIS GUILHERME; TEIXEIRA, ALINE FLORENCIO; TABET OLLER NASCIMENTO, ANA LUCIA. In Silico Structural and Functional Characterization of HtrA Proteins of Leptospira spp.: Possible Implications in Pathogenesis. TROPICAL MEDICINE AND INFECTIOUS DISEASE, v. 5, n. 4, DEC 2020. (18/21959-8, 17/06731-8, 16/11541-0, 14/50981-0)

FERNANDES, L. G., V; HORNSBY, R. L.; NASCIMENTO, A. L. T. O.; NALLY, J. E.. Application of CRISPR Interference (CRISPRi) for Gene Silencing in Pathogenic Species of Leptospira. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, v. N/A, n. 174, p. 14-pg., 2021-08-01. (17/06731-8, 14/50981-0, 19/20302-8)

TAKAHASHI, MARIA BEATRIZ; TEIXEIRA, ALINE FLORENCIO; NASCIMENTO, ANA LUCIA TABET OLLER. Overcoming problems to produce the recombinant protein LipL21 of Leptospira interrogans. BIOTECHNIQUES, v. N/A, p. 6-pg., 2023-04-17. (14/50981-0, 19/17488-2, 17/26223-7, 16/11541-0)

TEIXEIRA, ALINE F.; FERNANDES, LUIS G. V.; SOUZA FILHO, ANTONIO; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; NASCIMENTO, ANA L. T. O.. Evaluation of Lsa46 and Lsa77 Leptospiral Proteins for Their Immunoprotective Activities in Hamster Model of Leptospirosis. BIOMED RESEARCH INTERNATIONAL, v. 2018, p. 13-pg., 2018-01-01. (14/50981-0, 16/11541-0, 17/06731-8)

NASCIMENTO FILHO, EDSON G.; VIEIRA, MONICA L.; TEIXEIR, ALINE F.; SANTOS, JADEMILSON C.; FERNANDES, LUIS G. V.; PASSALIA, FELIPE J.; DAROZ, BRENDA B.; ROSSINI, AMANDA; KOCHI, LEANDRO T.; CAVENAGUE, MARIA F.; et al. Proteomics as a tool to understand Leptospira physiology and virulence: Recent advances, challenges and clinical implications. JOURNAL OF PROTEOMICS, v. 180, p. 8-pg., 2018-05-30. (14/50981-0, 17/01411-5, 17/01102-2, 16/01384-5, 16/04295-3, 16/11541-0, 17/06731-8)

FERNANDES, LUIS G. V.; FILHO, ANTONIO F. S.; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; ROMERO, ELIETE C.; NASCIMENTO, ANA L. T. O.. Decrease in antithrombin III and prothrombin serum levels contribute to coagulation disorders during leptospirosis. MICROBIOLOGY-SGM, v. 162, n. 8, p. 1407-1421, AUG 2016. (14/50981-0, 12/23913-9, 12/24164-0)

FIGUEREDO, JUPCIANA M.; SIQUEIRA, GABRIELA H.; DE SOUZA, GISELE O.; HEINEMANN, MARCOS B.; VASCONCELLOS, SILVIO A.; CHAPOLA, ERICA G. B.; NASCIMENTO, ANA L. T. O.. Characterization of two new putative adhesins of Leptospira interrogans. MICROBIOLOGY-SGM, v. 163, n. 1, p. 37-51, JAN 2017. (14/50981-0, 12/23913-9)

VIEIRA, MONICA L.; DE ANDRADE, SONIA A.; MORAIS, ZENAIDE M.; VASCONCELLOS, SILVIO A.; DAGLI, MARIA LUCIA Z.; NASCIMENTO, ANA LUCIA T. O.. Leptospira Infection Interferes with the Prothrombinase Complex Assembly during Experimental Leptospirosis. FRONTIERS IN MICROBIOLOGY, v. 8, MAR 28 2017. (14/50981-0, 12/23913-9, 12/50523-7)

TEIXEIRA, ALINE F.; CAVENAGUE, MARIA F.; KOCHI, LEANDRO T.; FERNANDES, LUIS G.; SOUZA, GISELE O.; DE SOUZA FILHO, ANTONIO FRANCISCO; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS BRYAN; NASCIMENTO, ANA L. T. O.. Immunoprotective Activity Induced by Leptospiral Outer Membrane Proteins in Hamster Model of Acute Leptospirosis. FRONTIERS IN IMMUNOLOGY, v. 11, OCT 30 2020. (14/50981-0, 17/06731-8, 18/09652-4, 18/08131-0, 16/11541-0)

VIEIRA, MONICA LARUCCI; NASCIMENTO, ANA LUCIA T. O.. VirulentLeptospira interrogansInduce Cytotoxic Effects in Human Plateletsin vitroThrough Direct Interactions. FRONTIERS IN MICROBIOLOGY, v. 11, SEP 24 2020. (14/50981-0, 18/07054-2)

SANTOS, JADEMILSON C.; HANDA, SUMIT; FERNANDES, LUIS G. V.; BLEICHER, LUCAS; GANDIN, CESAR A.; DE OLIVEIRA-NETO, MARIO; GHOSH, PARTHO; NASCIMENTO, ANA LUCIA T. O.. Structural and biochemical characterization of Leptospira interrogans Lsa45 reveals a penicillin-binding protein with esterase activity. Process Biochemistry, v. 125, p. 13-pg., 2022-12-22. (14/50981-0, 17/25167-6, 18/20321-0, 19/17488-2, 17/06731-8)

PASSALIA, FELIPE JOSE; HEINEMANN, MARCOS BRYAN; VIEIRA, MONICA LARUCCI; NASCIMENTO, ANA LUCIA T. O.. A Novel Leptospira interrogans Protein LIC13086 Inhibits Fibrin Clot Formation and Interacts With Host Components. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, JUL 1 2021. (17/01102-2, 18/07054-2, 17/00236-5, 14/50981-0, 19/17488-2)

KOCHI, LEANDRO T.; FERNANDES, V, LUIS G.; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; ROMERO, ELIETE C.; KIRCHGATTER, KARIN; NASCIMENTO, ANA L. T. O.. The interaction of two novel putative proteins of Leptospira interrogans with E-cadherin, plasminogen and complement components with potential role in bacterial infection. VIRULENCE, v. 10, n. 1, p. 734-753, JAN 1 2019. (16/01384-5, 17/06731-8, 14/50981-0)

FERNANDES, L. G. V.; GUAMAN, L. P.; VASCONCELLOS, S. A.; HEINEMANN, MARCOS B.; PICARDEAU, M.; NASCIMENTO, A. L. T. O.. Gene silencing based on RNA-guided catalytically inactive Cas9 (dCas9): a new tool for genetic engineering in Leptospira. SCIENTIFIC REPORTS, v. 9, FEB 12 2019. (17/06731-8, 14/50981-0)

VIEIRA, MONICA L.; PERSSON, SANDRA; LOPES-FERREIRA, MONICA; ROMERO, ELIETE C.; KIRCHGATTER, KARIN; NASCIMENTO, ANA LUCIA T. O.; HERWALD, HEIKO. Heparin-Binding Protein Release Is Strongly Induced by Leptospira Species and Is a Candidate for an Early Diagnostic Marker of Human Leptospirosis. Journal of Infectious Diseases, v. 219, n. 6, p. 996-1006, MAR 15 2019. (14/18337-4, 14/50981-0, 18/07054-2)

SIQUEIRA, GABRIELA H.; DE SOUZA, GISELE O.; HEINEMANN, MARCOS B.; VASCONCELLOS, SILVIO A.; NASCIMENTO, ANA L. T. O.. The role of Lsa23 to mediate the interaction of Leptospira interrogans with the terminal complement components pathway. Microbial Pathogenesis, v. 112, p. 182-189, NOV 2017. (14/50981-0, 14/03792-8)

CAVENAGUE, MARIA F.; TEIXEIRA, ALINE F.; FILHO, ANTONIO S.; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; NASCIMENTO, ANA L. T. O.. Characterization of a novel protein of Leptospira interrogans exhibiting plasminogen, vitronectin and complement binding properties. INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY, v. 309, n. 2, p. 116-129, MAR 2019. (16/11541-0, 14/50981-0, 16/04295-3)

FERNANDES, LUIS G. V.; TEIXEIRA, ALINE F.; FILHO, ANTONIO F. S.; SOUZA, GISELE O.; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; ROMERO, ELIETE C.; NASCIMENTO, ANA L. T. O.. Immune response and protective profile elicited by a multi-epitope chimeric protein derived from Leptospira interrogans. INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, v. 57, p. 61-69, APR 2017. (12/01797-7, 12/23913-9, 14/50981-0)

SANTOS, JADSON V.; PEREIRA, PRISCILA R. M.; FERNANDES, LUIS G. V.; SIQUEIRA, GABRIELA HASE; DE SOUZA, GISELE O.; SOUZA FILHO, ANTONIO; VASCONCELLOS, SILVIO A.; HEINEMANN, MARCOS B.; CHAPOLA, ERICA G. B.; NASCIMENTO, ANA L. T. O.. Binding of human plasminogen by the lipoprotein LipL46 of Leptospira interrogans. MOLECULAR AND CELLULAR PROBES, v. 37, p. 10-pg., 2018-02-01. (15/02590-5, 14/50981-0, 12/24164-0)