Echinococcus multilocularis phosphoglucose isomerase (EmPGI): a glycolytic enzyme involved in metacestode growth and parasite-host cell interactions.
In Echinococcus multilocularis metacestodes, the surface-associated and highly glycosylated laminated layer, and molecules associated with this structure, is believed to be involved in modulating the host-parasite interface. We report on the molecular and functional characterisation of E. multilocularis phosphoglucose isomerase (EmPGI), which is a component of this laminated layer. The EmPGI amino acid sequence is virtually identical to that of its homologue in Echinococcus granulosus, and shares 64% identity and 86% similarity with human PGI. Mammalian PGI is a multi-functional protein which, besides its glycolytic function, can also act as a cytokine, growth factor and inducer of angiogenesis, and plays a role in tumour growth, development and metastasis formation. Recombinant EmPGI (recEmPGI) is also functionally active as a glycolytic enzyme and was found to be present, besides the laminated layer, in vesicle fluid and in germinal layer cell extracts. EmPGI is released from metacestodes and induces a humoral immune response in experimentally infected mice, and vaccination of mice with recEmPGI renders these mice more resistant towards secondary challenge infection, indicating that EmPGI plays an important role in parasite development and/or in modulating the host-parasite relationship. We show that recEmPGI stimulates the growth of isolated E. multilocularis germinal layer cells in vitro and selectively stimulates the proliferation of bovine adrenal cortex endothelial cells but not of human fibroblasts and rat hepatocytes. Thus, besides its role in glycolysis, EmPGI could also act as a factor that stimulates parasite growth and potentially induces the formation of novel blood vessels around the developing metacestode in vivo.
Stadelmann
Britta
B
Institute of Parasitology, Vetsuisse Faculty, University of Berne, Berne, Switzerland. britta.stadelmann@ipa.unibe.ch
Spiliotis
Markus
M
Müller
Joachim
J
Scholl
Sabrina
S
Müller
Norbert
N
Gottstein
Bruno
B
Hemphill
Andrew
A
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D002417:Cattle; D002460:Cell Line; D049109:Cell Proliferation; D018509:DNA, Helminth / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D004443:Echinococcosis / Q000276:immunology / Q000517:prevention & control; D048209:Echinococcus granulosus / Q000201:enzymology / Q000235:genetics; D048210:Echinococcus multilocularis / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006019:Glycolysis; D006790:Host-Parasite Interactions; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D051381:Rats; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014611:Vaccination / Q000379:methods; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000909:Antibodies, Helminth; D018509:DNA, Helminth; D037521:Virulence Factors; D005956:Glucose-6-Phosphate Isomerase