Leptospira Infection Interferes with the Prothrombinase Complex Assembly during Experimental Leptospirosis

Autor(es)

Vieira, Monica L. ; de Andrade, Sonia A. ; Morais, Zenaide M. ; Vasconcellos, Silvio A. ; Dagli, Maria Lucia Z. ; Nascimento, Ana Lucia T. O.

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN MICROBIOLOGY; v. 8, MAR 28 2017.
• Citações Web of Science: 0

Resumo

Leptospirosis is a worldwide zoonotic and neglected infectious disease of human and veterinary concern, caused by pathogenic Leptospira species. 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 with L. interrogans. The lungs, kidneys, and livers were collected for culture, histopathology, and coagulation assays. L. interrogans infection 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. (AU)

• 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: 12/23913-9 - Identificação e caracterização de proteínas de Leptospira interrogans envolvidas nas interações patógeno - hospedeiro
• Beneficiário: Ana Lucia Tabet Oller do Nascimento
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/50523-7 - Clonagem, expressão, purificação e caracterização de termolisinas de Leptospira interrogans: interações com o sistema plasminogênio / plasmina e implicações na infecção
• Beneficiário: Mônica Larucci Vieira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado