Biochemical and immunological evaluation of hypothetical surface proteins of Leptospira interrogans

• Grant number: 17/01102-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: May 01, 2017
• End date: April 30, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ana Lucia Tabet Oller do Nascimento
• Grantee: Felipe José Passalia
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 14/50981-0 - Search for surface proteins among the genome sequences of Leptospira interrogans: functional and immunological characterization to understanding mechanisms involved in the bacterial pathogenesis, AP.TEM
• Associated scholarship(s): 20/02678-8 - Biochemical and immunological evaluation of hypothetical surface proteins of Leptospira interrogans, BE.EP.DD

Abstract

Leptospirosis is a zoonosis of global importance that has been considered one of the leading emerging infectious diseases in the last ten years. It is caused by a group of pathogenic bacteria of the genus Leptospira (Bharti et al., 2003). In urban centers, rodents play the major reservoirs of the disease by allowing the colonization of leptospires in the proximal renal tubules and excreting them alive in the urine. Due to the wide spectrum of symptoms that the patient may present with an inefficient diagnosis of the disease, the number of cases in the world remains underestimated. There is no effective vaccine so far. The identification of outer membrane proteins conserved among pathogenic strains are the main research targets to elucidate pathogenicity mechanisms. Using the genome sequences of L. interrogans and bioinformatics tools, our group identified a number of diverse membrane proteins with a potential role in the pathogenicity of this bacterium including new adhesins and candidate proteins for the diagnosis of the disease. Therefore, the present project proposes: (i) to clone, express and purify 2 new predicted membrane proteins; (ii) to evaluate the interaction capacity with extracellular matrix components; (iii) to evaluate the ability to interact with the PLG/PLA fibrinolytic system and possible implications for the infection; (iv) to study the interaction between complement system regulators and terminal complement components; (v) evaluating the diagnostic and immunoprotective potential. These studies will contribute to the knowledge of the pathogenesis of leptospires and identify candidates for vaccine development and/or for the early diagnosis of the disease. (AU)

Scientific publications

(7)

(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)

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)

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)

PASSALIA, FELIPE JOSE; HEINEMANN, MARCOS BRYAN; DE ANDRADE, SONIA APARECIDA; NASCIMENTO, ANA LUCIA T. O.; VIEIRA, MONICA LARUCCI. Leptospira interrogans Bat proteins impair host hemostasis by fibrinogen cleavage and platelet aggregation inhibition. MEDICAL MICROBIOLOGY AND IMMUNOLOGY, v. 209, n. 2, FEB 2020. (17/00236-5, 18/07054-2, 17/01102-2)

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)

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)

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)

DAROZ, BRENDA B.; FERNANDES, LUIS G. V.; CAVENAGUE, MARIA F.; KOCHI, LEANDRO T.; PASSALIA, FELIPE J.; TAKAHASHI, MARIA B.; NASCIMENTO FILHO, EDSON G.; TEIXEIRA, ALINE F.; NASCIMENTO, ANA L. T. O.. A Review on Host-Leptospira Interactions: What We Know and Future Expectations. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, p. 13-pg., 2021-11-25. (18/06201-1, 18/08131-0, 17/01102-2, 17/26223-7, 16/11541-0, 18/09652-4, 18/21959-8, 19/17488-2, 17/06731-8)