Leptospira interrogans Bat proteins impair host hemostasis by fibrinogen cleavage and platelet aggregation inhibition

Autor(es)

Passalia, Felipe Jose ^{[1, 2]} ; Heinemann, Marcos Bryan ^[3] ; de Andrade, Sonia Aparecida ^[4] ; Nascimento, Ana Lucia T. O. ^{[1, 2]} ; Vieira, Monica Larucci ^{[5, 1]}

Afiliação do(s) autor(es)

^[1] Inst Butantan, Lab Desenvolvimento Vacinas, Sao Paulo - Brazil

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

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

^[4] Inst Butantan, Lab Especial Dor & Sinalizacao Celular, Sao Paulo - Brazil

^[5] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MEDICAL MICROBIOLOGY AND IMMUNOLOGY; v. 209, n. 2 FEB 2020.
• Citações Web of Science: 2

Resumo

Leptospirosis is a worldwide spread zoonosis, caused by pathogenic Leptospira. Evidences suggest that compromised hemostasis might be involved in the leptospirosis pathophysiology. In the genome of L. interrogans serovar Copenhageni, we found two genes coding for proteins which comprise von Willebrand factor (VWF) A domains (BatA and BatB). As VWF A domains exhibit multiple binding sites which contributes to human VWF hemostatic functions, we hypothesized that the L. interrogans BatA and BatB proteins could be involved in the hemostatic impairment during leptospirosis. We have cloned, expressed in Escherichia coli, and purified recombinant BatA and BatB. The influence of recombinant BatA and BatB on different in vitro hemostatic assays evaluating the enzymatic activity, platelet aggregation and fibrinogen integrity was investigated. We describe BatB as a new serine protease which is able to cleave thrombin chromogenic substrate, fibrin, fibrinogen, gelatin and casein; while BatA is active only towards fibrinogen. BatA and BatB interfere with the platelet aggregation induced by VWF/ristocetin and thrombin. Our results suggest an important role of the L. interrogans serovar Copenhageni Bat proteins in the hemostasis dysfunction observed during leptospirosis and contribute to the understanding of the leptospirosis pathophysiological mechanisms. (AU)

• Processo FAPESP: 17/00236-5 - As plaquetas na interface da modulação da imunidade, inflamação e hemostasia na leptospirose
• Beneficiário: Mônica Larucci Vieira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 18/07054-2 - As plaquetas na interface da modulação da imunidade, inflamação e hemostasia na leptospirose
• Beneficiário: Mônica Larucci Vieira
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 17/01102-2 - Caracterização bioquímica e imunológica de proteínas hipotéticas de superfície de Leptospira interrogans
• Beneficiário: Felipe José Passalia
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto