Structural characterization of surface proteins of Leptospira interrogans and thermodynamics of the interaction with host-components

• Grant number: 17/25167-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2018
• End date: January 14, 2020
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ana Lucia Tabet Oller do Nascimento
• Grantee: Jademilson Celestino dos Santos
• 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): 18/20321-0 - Structural characterization of surface proteins of Leptospira interrogans - A view of pathogen-host interactions, BE.EP.PD

Abstract

Leptospirosis is a zoonotic disease distributed in practically all continents, with a high prevalence in tropical and subtropical regions. In developed countries, leptospirosis has a low incidence in humans and is mostly related to occupational or recreational activities associated with water. In these countries leptospirosis causes a negative economic impact in the agroindustry, because the disease can affect the livestock. It is estimated that each year more than 1 million cases of leptospirosis are reported in humans with approximately 60,000 annual deaths. The etiological agents of leptospirosis are pathogenic species of the genus Leptospira. Although clinical aspects and progression of leptospirosis in humans and animals are well described, little is known about the molecular aspects related to the specific mechanisms of virulence and pathogenicity. This lack of molecular information has limited the development of efficient vaccines or serodiagnostics. It is believed that it is on the outer membrane (OM) of the pathogenic species of Leptospira that the main factors of pathogenicity and virulence are found. Our group identified more than 200 genes of L. interrogans that encode proteins associated with OM. These proteins have been evaluated as potential vaccine or serodiagnostics candidates over the years. Two cloned proteins in our group were selected in an attempt to explain the mechanism of pathogenesis of L. interrogans to human host. These two proteins: Lsa63 and Lsa45 have been described as proteins that interact with extracellular matrix components (ECM) and human plasma. Such interactions are essential for infection and dissemination of the bacteria to the host. This work brings novel methodological approach to the "Functional Genomics of L. interrogans" research line, such as protein crystallography and molecular biophysics, to characterize structurally and thermodynamically the pathogen-host interactions.

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)

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)

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)

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)