Binding of human plasminogen by the lipoprotein LipL46 of Leptospira interrogans

Autor(es)

Santos, Jadson V. ; Pereira, Priscila R. M. ; Fernandes, Luis G. V. ; Siqueira, Gabriela Hase ; de Souza, Gisele O. ; Souza Filho, Antonio ; Vasconcellos, Silvio A. ; Heinemann, Marcos B. ; Chapola, Erica G. B. ; Nascimento, Ana L. T. O.

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR AND CELLULAR PROBES; v. 37, p. 10-pg., 2018-02-01.

Resumo

Leptospirosis is a widespread zoonosis caused by pathogenic Leptospira. Bacteria disseminate via the bloodstream and colonize the renal tubules of reservoir hosts. Leptospiral surface-exposed proteins are important targets, because due to their location they can elicit immune response and mediate adhesion and invasion processes. LipL46 has been previously reported to be located at the leptospiral outer membrane and recognized by antibodies present in serum of infected hamsters. In this study, we have confirmed the cellular location of this protein by immunofluorescence and FACS. We have cloned and expressed the recombinant protein LipL46 in its soluble form. LipL46 was recognized by confirmed leptospirosis human serum, suggesting its expression during infection. Binding screening of LipL46 with extracellular matrix (ECM) and plasma components showed that this protein interacts with plasminogen. The binding is dose-dependent on protein concentration, but saturation was not reached with the range of protein concentration used. Kringle domains of plasminogen and lysine residues of the recombinant protein are involved in the binding because the lysine analog, amino caproic acid (ACA) almost totally inhibited the reaction. The interaction of LipL46 with plasminogen generates plasmin in the presence of plasminogen activator uPA. Because plasmin generated at the leptospiral surface can degrade ECM molecules and decrease opsonophagocytosis, we tentatively infer that Lip46 has a role in helping the invasion process of pathogenic Leptospira. (AU)

• Processo FAPESP: 15/02590-5 - Caracterização imunogênica e funcional de duas lipoproteínas preditas de Leptospira interrogans expressas em Escherichia coli
• Beneficiário: Priscila Romero Mazzini Pereira
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 14/50981-0 - Busca de proteínas de superfície nas sequências do genoma da Leptospira interrogans: caracterização funcional e imunológica para o entendimento de mecanismos envolvidos na patogênese de bactéria
• Beneficiário: Ana Lucia Tabet Oller do Nascimento
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/24164-0 - Caracterização da interação de Leptospira interrogans com o sistema protrombina/trombina e possíveis implicações na virulência
• Beneficiário: Luis Guilherme Virgílio Fernandes
• Modalidade de apoio: Bolsas no Brasil - Doutorado