Schistosoma mansoni phosphoglycerate mutase: a glycolytic ectoenzyme with thrombolytic potential.

Autor: Pirovich DB; Molecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, MA 01536, USA., Da'dara AA; Molecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, MA 01536, USA., Skelly PJ; Molecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, MA 01536, USA.
Jazyk: angličtina
Zdroj: Parasite (Paris, France) [Parasite] 2022; Vol. 29, pp. 41. Date of Electronic Publication: 2022 Sep 09.
DOI: 10.1051/parasite/2022042
Abstrakt: Schistosomiasis is a debilitating parasitic disease caused by intravascular flatworms called schistosomes (blood flukes) that affects >200 million people worldwide. Proteomic analysis has revealed the surprising presence of classical glycolytic enzymes - typically cytosolic proteins - located on the extracellular surface of the parasite tegument (skin). Immunolocalization experiments show that phosphoglycerate mutase (PGM) is widely expressed in parasite tissues and is highly expressed in the tegument. We demonstrate that live Schistosoma mansoni parasites express enzymatically active PGM on their tegumental surface. Suppression of PGM using RNA interference (RNAi) diminishes S. mansoni PGM (SmPGM) gene expression, protein levels, and surface enzyme activity. Sequence comparisons place SmPGM in the cofactor (2,3-bisphosphoglycerate)-dependent PGM (dPGM) family. We have produced recombinant SmPGM (rSmPGM) in an enzymatically active form in Escherichia coli. The Michaelis-Menten constant (K m ) of rSmPGM for its glycolytic substrate (3-phosphoglycerate) is 0.85 mM ± 0.02. rSmPGM activity is inhibited by the dPGM-specific inhibitor vanadate. Here, we show that rSmPGM not only binds to plasminogen but also promotes its conversion to an active form (plasmin) in vitro. This supports the hypothesis that host-interactive tegumental proteins (such as SmPGM), by enhancing plasmin formation, may help degrade blood clots around the worms in the vascular microenvironment and thus promote parasite survival in vivo.
(© D.B. Pirovich et al., published by EDP Sciences, 2022.)
Databáze: MEDLINE
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