Characterization of a novel protein of Leptospira interrogans exhibiting plasminogen, vitronectin and complement binding properties

Autor(es)

Cavenague, Maria F. ^{[1, 2]} ; Teixeira, Aline F. ^[1] ; Filho, Antonio S. ^[3] ; Souza, Gisele O. ^[3] ; Vasconcellos, Silvio A. ^[3] ; Heinemann, Marcos B. ^[3] ; Nascimento, Ana L. T. O. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Inst Butantan, Lab Especial Desenvolvimento Vacinas, Ctr Biotecnol, Ave Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Programa Posgrad Interunidades Biotecnol, Inst Ciencias Biomed, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Lab Zoonoses Bacterianas, Fac Med Vet & Zootecnia, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY; v. 309, n. 2, p. 116-129, MAR 2019.
• Citações Web of Science: 2

Resumo

Leptospirosis is a severe zoonosis caused by pathogenic species of the genus Leptospira. This work focuses on a hypothetical protein of unknown function, encoded by the gene LIC13259, and predicted to be a surface protein, widely distributed among pathogenic leptospiral strain. The gene was amplified from L. interrogans serovar Copenhageni, strain Fiocruz L1-130, cloned and the protein expressed using Escherichia coil as a host system. Immunofluorescence assay showed that the protein is surface-exposed. The recombinant protein LIC13259 (rLIC13259) has the ability to interact with the extracellular matrix (ECM) laminin, in a dose-dependent manner but saturation was not reach. The rLIC13259 protein is a plasminogen (PLG)-binding protein, generating plasmin, in the presence of urokinase PLG-activator uPA. The recombinant protein is able to mediate the binding to human purified terminal complement route vitronectin, C7, C8 and C9, and to recruit and interact with these components from normal human serum (NHS). These interactions are dose-dependent on NHS increased concentration. The binding of rLIC13259 to C8 and vitronectin was slight and pronounced inhibited in the presence of increasing heparin concentration, respectively, suggesting that the interaction with vitronectin occurs via heparin domain. Most interesting, the interaction of rLIC13259 with C9 protein was capable of preventing C9 polymerization, suggesting that the membrane attack complex (MAC) formation was inhibited. Thus, we tentatively assign the coding sequence (CDS) LIC13259, previously annotated as unknown function, as a novel protein that may play an important role in the host's invasion and immune evasion processes, contributing to the establishment of the leptospiral infection. (AU)

• 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: 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: 16/04295-3 - Interação de duas proteínas de Leptospira interrogans a componentes do plasma e matriz extracelular do hospedeiro
• Beneficiário: Maria Fernanda Cavenague Pereira
• Modalidade de apoio: Bolsas no Brasil - Mestrado