title: LeptospiraInfection Interferes with the Prothrombinase Complex Assembly during Experimental Leptospirosis.
abstract: Leptospirosis is a worldwide zoonotic and neglected infectious disease of human and veterinary concern, caused by pathogenicLeptospiraspecies. Although bleeding is a common symptom of severe leptospirosis, the cause of hemorrhage is not completely understood. In severe infections, modulation of hemostasis by pathogens is an important virulence mechanism, and hemostatic impairments such as coagulation/fibrinolysis dysfunction are frequently observed. Here, we analyze the coagulation status of experimentally infected hamsters in an attempt to determine coagulation interferences and the origin of leptospirosis hemorrhagic symptomatology. Hamsters were experimentally infected withL. interrogans. The lungs, kidneys, and livers were collected for culture, histopathology, and coagulation assays.L. interrogansinfection disturbs normal coagulation in the organs of animals. Our results suggest the presence of a thrombin-like factor or FX activator, which is able to activate FII in the leptospirosis organ extracts. The activity of those factors is accelerated in the prothrombinase complex. Additionally, we show for the first time that live leptospires act as a surface for the prothrombinase complex assembly. Our results contribute to the understanding of leptospirosis pathophysiological mechanisms and may open new routes for the discovery of novel treatments in the severe manifestations of the disease.
authors.affiliation: Laboratorio Especial de Desenvolvimento de Vacinas, Instituto Butantan São Paulo, Brazil.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Vieira
authors.affiliation: Laboratório de Síntese Orgânica - Laboratório Especial de Toxinologia Aplicada São Paulo, Brazil.
authors.forename: Sonia A
authors.initials: SA
authors.lastname: de Andrade
authors.affiliation: Laboratório de Zoonoses Bacterianas, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo São Paulo, Brazil.
authors.forename: Zenaide M
authors.initials: ZM
authors.lastname: Morais
authors.affiliation: Laboratório de Zoonoses Bacterianas, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo São Paulo, Brazil.
authors.forename: Silvio A
authors.initials: SA
authors.lastname: Vasconcellos
authors.affiliation: Departmento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo São Paulo, Brazil.
authors.forename: Maria Lucia Z
authors.initials: ML
authors.lastname: Dagli
authors.affiliation: Laboratorio Especial de Desenvolvimento de Vacinas, Instituto ButantanSão Paulo, Brazil; Programa de Pós-Graduação Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, Universidade de São PauloSão Paulo, Brazil.
authors.forename: Ana Lucia T O
authors.initials: AL
authors.lastname: Nascimento
keywords: Leptospira; coagulation; hemostasis; leptospirosis; prothrombinase complex