Advanced search
Start date

Advancing the understanding of pathogenesis and virulence of Leptospira interrogans through proteomics, structural, mutagenesis and immunological analyses

Grant number: 19/17488-2
Support Opportunities:Research Projects - Thematic Grants
Duration: December 01, 2020 - November 30, 2025
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
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
Pesquisadores principais:
Daniel Carvalho Pimenta
Associated researchers:Alexandre Paulo Yague Lopes ; Aline Rodrigues Florêncio Teixeira ; Eliete Caló Romero ; Giovana Cappio Barazzone ; Gisele Oliveira de Souza ; Jademilson Celestino dos Santos ; Luis Guilherme Virgílio Fernandes ; Marcos Bryan Heinemann ; Mônica Larucci Vieira ; Silvio Arruda Vasconcellos
Associated scholarship(s):22/16481-7 - Obtaining Leucine Rich Repeats (LRR) protein mutants in Leptospira interrogans and phenotypic evaluation of Host-pathogen interactions, BP.DD
22/12101-5 - Expression of multifunctional protein Lsa23 (LIC11360) from Leptospira interrogans in the surrogate saprophyte L. biflexa and gain of function validation, BP.PD
22/08985-5 - Assessment of the role of two proteins of Leptospira interrogans in the pathogenesis and in the immunoprotective activity in animal model, BP.DD
17/06731-8 - Application of CRISPR-interference for elucidating leptospirosis pathogenesis and development of novel strategies for knockout mutant's obtainment, BP.PD
16/11541-0 - Evaluation of the vaccine potential of antigenic fractions obtained in Leptospira interrogans serovar Copenhageni using hamsters as an animal model, BP.PD


Leptospirosis is a zoonosis widely distributed in all continents, but prevalent in tropical and sub-tropical regions. The etiological agent is the pathogenic bacteria of the genus Leptospira. In developed countries, the disease in humans is associated with recreational activities with water, while in developing ones, the disease represents a public health problem, with 1 million cases reported being fatal cases around 60 thousands per year. In all countries, leptospirosis has an economic impact because it affects the livestock, causing loss of milk production, failure to thrive and premature death. In urban areas, the rodents, such as Rattus norvegicus, are the main reservoir of the disease. They are asymptomatic carriers of the bacteria, keeping shedding them live through the urine for their lifetime, contaminating soil and water. In Brazil, outbreaks of leptospirosis occur during the rainy season when flooding are frequent. Inundation in association with precarious sanitary conditions favors the contact of humans with contaminated water, spreading the disease. The symptoms of the disease are non-specific flu-like and include fever, headache and myalgia. In some cases, the disease evolves to severe forms, called Well's syndrome and Severe Pulmonary Hemorrhagic Syndrome- SPHS, with mortality rates in adults of 10 to 50% of the cases. There are no efficient diagnostic methods available. Because sanitary measures and rat eradication are difficult to implement, the adoption of prophylactic actions is the best choice to fight the disease. Therefore, different research groups around the world are pursuing the development of vaccine. Understanding the mechanisms of pathogenicity and the identification of virulent factors are crucial to block this pathogen. In this sense, the present project proposes distinctive methodological approaches aiming to advance the knowledge of these bacteria in different aspects: comparative proteomics analysis, structural biochemistry for the recombinant proteins available in our laboratory, mutants knock-in of saprophyte strain and gene silencing of pathogenic strain by CRISPR Cas9 method, scale-up of recombinant protein purification process for diagnostic kit development; to evaluate the involvement of the leptospiral proteins LipL41, LipL21, Lip46 and OmpL37, as potential receptor for endothelial and epithelial cultured cells in vitro. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
Articles published in other media outlets (0 total):
More itemsLess items

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)
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, . (17/26223-7, 19/17488-2, 17/00236-5)
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, . (17/01102-2, 18/07054-2, 17/00236-5, 14/50981-0, 19/17488-2)
FERNANDES, LUIS G. V.; PUTZ, ELLIE J.; STASKO, JUDITH; LIPPOLIS, JOHN D.; NASCIMENTO, ANA L. T. O.; NALLY, JARLATH E.. valuation of LipL32 and LigA/LigB Knockdown Mutants in Leptospira interrogans Serovar Copenhageni: Impacts to Proteome and Virulenc. FRONTIERS IN MICROBIOLOGY, v. 12, . (17/06731-8, 19/20302-8, 19/17488-2)

Please report errors in scientific publications list by writing to: