title: Schistosomes Enhance Plasminogen Activation: The Role of Tegumental Enolase.
abstract: Schistosoma mansoni is a blood fluke parasite that causes schistosomiasis, a debilitating disease of global public health importance. These relatively large parasites are able to survive prolonged periods in the human vasculature without inducing stable blood clots around them. We show here that the intravascular life stages (schistosomula and adult males and females) can all promote significant plasminogen (PLMG) activation in the presence of tissue plasminogen activator (tPA). This results in the generation of the potent fibrinolytic agent plasmin which could degrade blood clots forming around the worms in vivo. We demonstrate that S. mansoni enolase (SmEno) is a host-interactive tegumental enzyme that, in recombinant form, can bind PLMG and promote its activation. Like classical members of the enolase protein family, SmEno can catalyze the interconversion of 2-phospho-D-glycerate (2-PGA) and phosphoenolpyruvate (PEP). The enzyme has maximal activity at pH 7.5, requires Mg2+ for optimal activity and can be inhibited by NaF but not mefloquin. Suppressing expression of the SmEno gene significantly diminishes enolase mRNA levels, protein levels and surface enzyme activity but, surprisingly, does not affect the ability of the worms to promote PLMG activation. Thus, while SmEno can enhance PLMG activation, our analysis suggests that it is not the only contributor to the parasite's ability to perform this function. We show that the worms possess several other PLMG-binding proteins in addition to SmEno and these may have a greater importance in schistosome-driven PLMG activation.
authors.affiliation: Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, United States of America.|Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.|Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Ministério de Ciência Tecnologia e Inovação Salvador, Bahia, Brazil.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Figueiredo
authors.affiliation: Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, United States of America.
authors.forename: Akram A
authors.initials: AA
authors.lastname: Da'dara
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.|Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais (INCT-DT), Conselho Nacional de Desenvolvimento Científico e Tecnológico, Ministério de Ciência Tecnologia e Inovação Salvador, Bahia, Brazil.
authors.forename: Sergio C
authors.initials: SC
authors.lastname: Oliveira
authors.affiliation: Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, United States of America.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Skelly
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015801:Helminth Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D012550:Schistosoma mansoni / Q000201:enzymology*; D012555:Schistosomiasis mansoni / Q000201:enzymology*; D014162:Transfection
chemical_list: D015801:Helminth Proteins; D034741:RNA, Small Interfering; D010958:Plasminogen; D010751:Phosphopyruvate Hydratase