Evaluation of the functional role of two Leptospira interrogans proteins in the adhesion process of the pathogen to the host

• Grant number: 16/01384-5
• Support type: Scholarships in Brazil - Master
• Effective date (Start): July 01, 2016
• Effective date (End): February 28, 2018
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ana Lucia Tabet Oller Do Nascimento
• Grantee: Leandro Toshio Kochi
• Home 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

Abstract

Leptospirosis is a zoonosis of global importance, recently included in the list of neglected tropical diseases. In urban environments, rodents are the main reservoirs of the disease. Leptospires colonize the proximal renal tubules and are shedding alive in the urine. Up to date, there is no effective vaccine. The identification of conserved outer membrane proteins among different pathogenic strains is the main goal of research to elucidate the pathogenicity mechanisms. These proteins, probably involved in the interaction of leptospires with the environment, could also function as a target to the host immune system. Several research groups' pursuit the identification and characterization of surface proteins that are antigenic and conserved among various serovars of Leptospira interrogans. Thus, this project proposes to clone and express two predicted lipoproteins from Leptospira, coded by the genes LIC12587 and LIC11711. The recombinant proteins will be purified by metal-chelating chromatography and injected in mice for evaluating their immunogenic activity and obtaining immune sera. These sera will be employed for evaluating the presence of the native proteins in protein extracts of different serovars of Leptospira spp., for accessing their conservation and cellular location. The recombinant proteins will be evaluated regarding their reactivity with antibodies in human serum samples in confirmed cases of leptospirosis and their capability of interacting with human extracellular matrix and plasma components, and by so, evaluating the participation of the proteins in the adhesion process to the host. (AU (AU)

Scientific publications

(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, 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. Web of Science Citations: 1.

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. Web of Science Citations: 0.

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.; PIMENTA, DANIEL C.; NASCIMENTO, ANA L. T. O. 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. Web of Science Citations: 1.