LIC12254 Is a Leptospiral Protein That Interacts with Integrins via the RGD Motif

Autor(es)

Cavenague, Maria F. F. ; Teixeira, Aline F. F. ; Fernandes, Luis G. V. ; Nascimento, Ana L. T. O.

• Tipo de documento: Artigo Científico
• Fonte: TROPICAL MEDICINE AND INFECTIOUS DISEASE; v. 8, n. 5, p. 15-pg., 2023-04-26.

Resumo

Pathogenic leptospires can bind to receptors on mammalian cells such as cadherins and integrins. Leptospira effectively adheres to cells, overcomes host barriers and spreads into the bloodstream, reaching internal target organs such as the lungs, liver and kidneys. Several microorganisms produce proteins that act as ligands of integrins through the RGD motif. Here, we characterized a leptospiral RGD-containing protein encoded by the gene lic12254. In silico analysis of pathogenic, intermediate and saprophytic species showed that LIC12254 is highly conserved among pathogenic species,and is unique in presenting the RGD motif. The LIC12254-coding sequence is greatly expressed in the virulent Leptospira interrogans L1-130 strain compared with the culture-attenuated L. interrogans M20 strain. We also showed that the recombinant protein rLIC12254 binds to alpha V beta 8 and a8 human integrins most likely via the RGD motif. These interactions are dose-dependent and saturable, a typical property of receptor-ligand interactions. The binding of the recombinant protein lacking this motif-rLIC12254 Delta RAA-to alpha V beta 8 was almost totally abolished, while that with the a8 human integrin was decreased by 65%. Taken together, these results suggest that this putative outer membrane protein interacts with integrins via the RGD domain and may play a key role in leptospirosis pathogenesis. (AU)

• Processo FAPESP: 18/08131-0 - Expressão heteróloga do gene LIC13259 na cepa saprófita Leptospira biflexa e aquisição da capacidade de evasão do sistema imune humano
• Beneficiário: Maria Fernanda Cavenague Pereira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• 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: 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: 17/06731-8 - Aplicação de CRISPR-interferência na elucidação da patogênese da leptospirose e desenvolvimento de novas estratégias para obtenção de mutantes knockout
• Beneficiário: Luis Guilherme Virgílio Fernandes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado