Schistosomes Enhance Plasminogen Activation: The Role of Tegumental Enolase

Barbara C. Figueiredo1,2,3*, Akram A. Da'dara1, Sergio C. Oliveira2,3, Patrick J. Skelly1

PLOS Pathogens. December 11, 2015 | Volume 10 | Issue 1 | e1003901

Speaker: Chung-Ching Kuo (郭重慶)                          Time: 15:00~16:00, May. 04, 2016

Commentator: Jyh-Wei Shin, Ph.D. (辛致煒 教授)    Place: Room 601

Abstract:

Schistosoma mansoni is a blood fluke parasite that causes schistosomiasis, which is considered by the World Health Organization as the second most socioeconomically devastating parasitic disease with hundreds of millions infected worldwide. This large parasite is able to survive prolonged periods in the human vasculature without inducing stable blood clots around them. In the previous study revealed that plasminogen binds to the surface of male—but not female—S. bovis worms and that an extract of tegument proteins induces the generation of plasmin on its own and also enhances the plasmin generation induced by tissue-type plasminogen activator (t-PA). [1]. This study shows that the intravascular life stages (schistosomula and adult males and females) can all promote significant plasminogen (PLMG) activation in the presence of (tPA). The results shows that in the generation of the potent fibrinolytic agent plasmin which could degrade blood clots forming around the worms in vivo. Authors demonstrate that S. mansoni enolase (SmEno) is a host-interactive tegumental enzyme that, in recombinant form, can bind PLMG and promote its activation. SmEno can catalyze the interconversion of 2-phospho-D-glycerate (2-PGA) and phosphoenolpyruvate (PEP) like classical members of the enolase protein family. Suppressing expression of the SmEno gene significantly diminishes enolase mRNA levels, protein levels, and surface enzyme activity but does not affect the ability of the worms to promote PLMG activation. Therefore, Authors’ analysis suggests that it is not the only contributor to the parasite’s ability to perform this function. This study shows that the worms possess several other PLMG-binding proteins in addition to SmEno, which may have a greater importance in schistosome-driven PLMG activation.

References:

1.  Alicia Ramajo-Hernandez 1, Ricardo Perez-Sanchez 1, Vicente Ramajo-Martin, Ana Oleaga. Schistosoma bovis: Plasminogen binding in adults and the identification of plasminogen-binding proteins from the worm tegument. Experimental Parasitology 115 (2007) 83–91