Evaluation of functional role of Leptospira interrogans surface proteins as endothelial and epithelial cells receptors of the host

• Grant number: 17/26223-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: May 01, 2018
• End date: March 31, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ana Lucia Tabet Oller do Nascimento
• Grantee: Maria Beatriz Takahashi
• 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

Abstract

Leptospirosis is a widely disseminated zoonosis and occurs endemic in several parts of the world. In Brazil, the most frequent epidemics occur in poor communities during the rainy season, when constant flooding associated with precarious sanitation conditions favor contact with contaminated environment and water. Ways to control the spread of disease are scant. The understanding of the leptospires pathogenicity mechanisms is fundamental to block the action of this pathogen. Then, the identification of conserved outer membrane proteins are the main research targets, since this surface location facilitates interaction with the host. Several studies have tried to characterize the involvement of surface proteins of Leptospira interrogans with host components. Thus, the current project aims to evaluate the involvement of LipL41, LipL21, Lip46 and OmpL37 proteins as endothelial and epithelial cell receptors in vitro. The cloned genes will be expressed in E. coli strains. Recombinant proteins will be purified by metal affinity chromatography and analyzed for structure by the circular dichroism technique. BALB/c animals will be immunized with recombinant proteins to produce polyclonal antiserum and the sera obtained will be titrated by ELISA. Next, the recombinant proteins will be evaluated for reactivity with antibodies present in the sera of patients diagnosed with Leptospirosis and their interactions with endothelial and epithelial cells will be characterized in vitro. The accomplishment of these experimental stages will contribute to the identification of proteins involved in the pathogen-host interaction. (AU)

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)

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)

TAKAHASHI, M. B.; TEIXEIRA, A. F.; ALTO, NASCIMENTO. The leptospiral LipL21 and LipL41 proteins exhibit a broad spectrum of interactions with host cell components. VIRULENCE, v. 12, n. 1, p. 2798-2813, DEC 31 2021. (17/26223-7, 19/17488-2, 17/00236-5)

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)

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)