title: Leptospira interrogans reduces fibrin clot formation by modulating human thrombin activity via exosite I.
abstract: Pathogenic bacteria of the genus Leptospira are the etiological agents of leptospirosis, a disease that affects humans and animals worldwide. Although there are an increasing number of studies on the biology of Leptospira, the mechanisms of pathogenesis are not yet understood. We report in this work that Leptospira interrogans FIOCRUZ L1-130 virulent, M20 culture attenuated and the saprophyte L. biflexa Patoc 1 strains do not bind prothrombin. Leptospiral binding to thrombin was detected with the virulent, followed by culture-attenuated M20, and practically none was observed with the saprophyte strain. The interaction of Leptospira with thrombin mostly occurs via exosite I, with a minor participation of catalytic site, as determined by employing the thrombin inhibitors hirugen, hirudin and argatroban. Leptospira interrogans binding to thrombin inhibits its catalytic activity reducing fibrin clot formation in thrombin-catalyzed reaction of fibrinogen. This inhibition was more efficient with the virulent FIOCRUZ L1-130 than with the M20 culture attenuated, while none was seen with the saprophyte strain, suggesting that this binding might be important for bacterial virulence. This is the first study reporting the binding of pathogenic Leptospira to thrombin promoting a decrease in fibrin clotting that could lead to hemorrhage, helping bacteria dissemination.
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, São Paulo, SP 05503-900, Brazil Programa de Pós-Graduação Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, USP, São Paulo 05508-900, Brazil.
authors.forename: Luis G
authors.initials: LG
authors.lastname: Fernandes
authors.affiliation: Laboratório de Zoonoses Bacterianas do VPS, Faculdade de MedicinaVeterinária e Zootecnia da Universidade de São Paulo, São Paulo 05508-270, Brazil.
authors.forename: Zenaide M
authors.initials: ZM
authors.lastname: de Morais
authors.affiliation: Laboratório de Zoonoses Bacterianas do VPS, Faculdade de MedicinaVeterinária e Zootecnia da Universidade de São Paulo, São Paulo 05508-270, Brazil.
authors.forename: Silvio A
authors.initials: SA
authors.lastname: Vasconcellos
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, Avenida Vital Brazil, 1500, São Paulo, SP 05503-900, Brazil Programa de Pós-Graduação Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, USP, São Paulo 05508-900, Brazil ana.nascimento@butantan.gov.br.
authors.forename: Ana L T O
authors.initials: AL
authors.lastname: Nascimento
mesh_terms: D001777:Blood Coagulation; D005337:Fibrin / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007921:Leptospira interrogans / Q000502:physiology*; D011485:Protein Binding; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D005337:Fibrin; D013917:Thrombin
keywords: Leptospira; coagulation; hemorrhage; leptospirosis