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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: MEDICAL MICROBIOLOGY AND IMMUNOLOGY; v. 209, n. 2 FEB 2020.
• Web of Science Citations: 2

Abstract

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)

• FAPESP's process: 17/00236-5 - Platelets at the interface of immunity, inflammation and hemostasis modulation in leptospirosis
• Grantee: Mônica Larucci Vieira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/07054-2 - Platelets at the interface of immunity, inflammation and hemostasis modulation in leptospirosis
• Grantee: Mônica Larucci Vieira
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 17/01102-2 - Biochemical and immunological evaluation of hypothetical surface proteins of Leptospira interrogans
• Grantee: Felipe José Passalia
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)