In silico analysis and functional characterization of a leucine-rich repeat protein of Leptospira interrogans

Autor(es)

Gaspar, Joao P. ; Takahashi, Maria B. ; Teixeira, Aline F. ; Nascimento, Ana L. T. O.

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY; v. 316, p. 11-pg., 2024-09-03.

Resumo

Pathogenic spirochetes of the genus Leptospira are the causative agent of leptospirosis, a widely disseminated zoonosis that affects humans and animals. The ability of leptospires to quickly cross host barriers causing infection is not yet fully understood. Thus, understanding the mechanisms of pathogenicity is important to combat leptospiral infection. Outer membrane proteins are interesting targets to study as they are able to interact with host molecules. Proteins containing leucine-rich repeat (LRR) domains are characterized by the presence of multiple regions containing leucine residues and they have putative functions related to host-pathogen interactions. Hence, the present study aimed to clone and express the recombinant protein encoded by the LIC11098 gene, an LRR protein of L. interrogans serovar Copenhageni. In silico analyses predicted that the target protein is conserved among pathogenic strains of Leptospira, , having a signal peptide and multiple LRR domains. The DNA sequence encoding the LRR protein was cloned in frame into the pAE vector, expressed without mutations in Escherichia coli and purified by His-tag chromatography. Circular dichroism (CD) spectrum showed that the recombinant protein was predominantly composed of beta-sheets. A dose-dependent interaction was observed with cellular and plasma fibronectins, laminin and the complement system component C9, suggesting a possible role of the protein encoded by LIC11098 gene at the initial stages of infection. (AU)

• Processo FAPESP: 19/17488-2 - Avançando no entendimento da patogenicidade e virulência da Leptospira interrogans através de análises proteômicas, estruturais, mutagênicas e imunológicas
• Beneficiário: Ana Lucia Tabet Oller do Nascimento
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/05466-4 - Identificação de antígenos de leptospiras reconhecidos por células T gama/delta como alvo para o desenvolvimento de vacinas de nova geração
• Beneficiário: Aline Florencio Teixeira
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 16/11541-0 - Avaliação do potencial vacinal de frações antigênicas obtidas em Leptospira interrogans serovar Copenhageni utilizando hamster como modelo animal
• Beneficiário: Aline Florencio Teixeira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 23/08486-1 - "Caracterização estrutural, funcional e imunogênica de duas proteínas de Leptospira interrogans contendo domínios FecR"
• Beneficiário: João Pedro Gaspar Inácio
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/26223-7 - Avaliação do papel funcional de proteínas de superfície de Leptospira interrogans como receptores de células endoteliais e epiteliais do hospedeiro
• Beneficiário: Maria Beatriz Takahashi
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto