{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:45:49Z","timestamp":1790779549006,"version":"4.1.0"},"reference-count":53,"publisher":"EDP Sciences","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":251,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI056273"],"award-info":[{"award-number":["AI056273"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Parasite"],"accepted":{"date-parts":[[2022,8,28]]},"published-print":{"date-parts":[[2022]]},"abstract":"<jats:p>Schistosomiasis is a debilitating parasitic disease caused by intravascular flatworms called schistosomes (blood flukes) that affects\u00a0&gt;200 million people worldwide. Proteomic analysis has revealed the surprising presence of classical glycolytic enzymes \u2013 typically cytosolic proteins \u2013 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 <jats:italic>Schistosoma mansoni<\/jats:italic> parasites express enzymatically active PGM on their tegumental surface. Suppression of PGM using RNA interference (RNAi) diminishes <jats:italic>S. mansoni<\/jats:italic> 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 <jats:italic>Escherichia coli<\/jats:italic>. The Michaelis-Menten constant (<jats:italic>K<\/jats:italic><jats:sub>m<\/jats:sub>) of rSmPGM for its glycolytic substrate (3-phosphoglycerate) is 0.85\u00a0mM\u00a0\u00b1\u00a00.02. 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) <jats:italic>in vitro<\/jats:italic>. 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 <jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1051\/parasite\/2022042","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T08:26:53Z","timestamp":1662712013000},"page":"41","source":"Crossref","is-referenced-by-count":10,"title":["<i>Schistosoma mansoni<\/i> phosphoglycerate mutase: a glycolytic ectoenzyme with thrombolytic potential"],"prefix":"10.1051","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9501-2770","authenticated-orcid":false,"given":"David B.","family":"Pirovich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akram A.","family":"Da\u2019dara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Skelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"250","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"issue":"5","key":"R1","doi-asserted-by":"crossref","first-page":"BSR20180705","DOI":"10.1042\/BSR20180705","volume":"38","author":"Ay\u00f3n-N\u00fa\u00f1ez","year":"2018","journal-title":"Bioscience Reports"},{"key":"R2","doi-asserted-by":"crossref","first-page":"18831","DOI":"10.1074\/jbc.M111.323287","volume":"287","author":"Barthel","year":"2012","journal-title":"Journal of Biological Chemistry"},{"key":"R3","doi-asserted-by":"crossref","first-page":"5929","DOI":"10.1128\/JB.00159-07","volume":"189","author":"Candela","year":"2007","journal-title":"Journal of Bacteriology"},{"key":"R4","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/0006-291X(80)90088-1","volume":"96","author":"Carreras","year":"1980","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"R5","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.molbiopara.2007.06.002","volume":"155","author":"Cass","year":"2007","journal-title":"Molecular and Biochemical Parasitology"},{"key":"R6","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.imbio.2016.01.001","volume":"221","author":"Castiblanco-Valencia","year":"2016","journal-title":"Immunobiology"},{"issue":"3","key":"R7","doi-asserted-by":"crossref","first-page":"e993","DOI":"10.1371\/journal.pntd.0000993","volume":"5","author":"Castro-Borges","year":"2011","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"R8","unstructured":"Chaudhry R, Varacallo M. 2020. Biochemistry, glycolysis, in StatPearls. StatPearls Publishing: Treasure Island, FL."},{"key":"R9","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1016\/S0140-6736(13)61949-2","volume":"383","author":"Colley","year":"2014","journal-title":"Lancet (London, England)"},{"key":"R10","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1046\/j.1365-2958.2003.03390.x","volume":"47","author":"Crowe","year":"2003","journal-title":"Molecular Microbiology"},{"key":"R11","doi-asserted-by":"crossref","unstructured":"Da\u2019dara AA, Skelly PJ. 2015. Gene suppression in schistosomes using RNAi, in Parasite Genomics Protocols. Peacock C, Editor. Humana Press: New York, NY. p. 143\u2013164.","DOI":"10.1007\/978-1-4939-1438-8_8"},{"key":"R12","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.meegid.2012.02.005","volume":"12","author":"Dhamodharan","year":"2012","journal-title":"Infection, Genetics & Evolution"},{"issue":"12","key":"R13","doi-asserted-by":"crossref","first-page":"e1005335","DOI":"10.1371\/journal.ppat.1005335","volume":"11","author":"Figueiredo","year":"2015","journal-title":"PLoS Pathogens"},{"key":"R14","doi-asserted-by":"crossref","unstructured":"Fothergill-Gilmore L, Watson H. 1989. The phosphoglycerate mutases, in Advances in Enzymology and Related Areas of Molecular Biology. Meister A, Editor. John Wiley & Sons: New York, NY. p. 227\u2013313.","DOI":"10.1002\/9780470123089.ch6"},{"key":"R15","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S0014-5793(99)00910-2","volume":"455","author":"Fraser","year":"1999","journal-title":"FEBS Letters"},{"key":"R16","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.ijmm.2016.09.001","volume":"306","author":"Gr\u00fcndel","year":"2016","journal-title":"International Journal of Medical Microbiology"},{"key":"R17","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1128\/IAI.01071-15","volume":"84","author":"Gr\u00fcndel","year":"2016","journal-title":"Infection and Immunity"},{"key":"R18","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/S0140-6736(06)69440-3","volume":"368","author":"Gryseels","year":"2006","journal-title":"Lancet"},{"key":"R19","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1042\/bj3260321","volume":"326","author":"Hellwage","year":"1997","journal-title":"Biochemical Journal"},{"key":"R20","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1038\/ncomms2759","volume":"4","author":"Hitosugi","year":"2013","journal-title":"Nature Communications"},{"key":"R21","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S0079-6107(00)00007-9","volume":"73","author":"Jedrzejas","year":"2000","journal-title":"Progress in Biophysics and Molecular Biology"},{"key":"R22","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1016\/j.peptides.2011.10.021","volume":"32","author":"Karkowska-Kuleta","year":"2011","journal-title":"Peptides"},{"key":"R23","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.3390\/cells10102736","volume":"10","author":"Karkowska-Kuleta","year":"2021","journal-title":"Cells"},{"key":"R24","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1099\/mic.0.2007\/013235-0","volume":"154","author":"Kinnby","year":"2008","journal-title":"Microbiology"},{"key":"R25","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1074\/mcp.M500097-MCP200","volume":"4","author":"Knudsen","year":"2005","journal-title":"Molecular & Cellular Proteomics"},{"key":"R26","doi-asserted-by":"crossref","unstructured":"Lewis FA, Tucker MS. 2014. Schistosomiasis, in Digenetic Trematodes. Toledo R, Fried B, Editors. Springer: New York, NY. p. 47\u201375.","DOI":"10.1007\/978-1-4939-0915-5_3"},{"key":"R27","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"issue":"3","key":"R28","doi-asserted-by":"crossref","first-page":"e90796","DOI":"10.1371\/journal.pone.0090796","volume":"9","author":"Lopez","year":"2014","journal-title":"PLoS One"},{"key":"R29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-018-0013-8","volume":"4","author":"McManus","year":"2018","journal-title":"Nature Reviews Disease Primers"},{"key":"R30","first-page":"3191","volume":"54","author":"Milligan","year":"2011","journal-title":"Journal of Visualized Experiments"},{"key":"R31","doi-asserted-by":"crossref","first-page":"119","DOI":"10.2147\/RRTM.S274518","volume":"11","author":"Molehin","year":"2020","journal-title":"Research and Reports in Tropical Medicine"},{"key":"R32","doi-asserted-by":"crossref","first-page":"e0007951","DOI":"10.1371\/journal.pntd.0007951","volume":"14","author":"Nation","year":"2020","journal-title":"PLOS Neglected Tropical Diseases"},{"key":"R33","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/nchembio.2453","volume":"13","author":"Oslund","year":"2017","journal-title":"Nature Chemical Biology"},{"key":"R34","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ccr.2014.12.002","volume":"301","author":"Pessoa","year":"2015","journal-title":"Coordination Chemistry Reviews"},{"issue":"3","key":"R35","doi-asserted-by":"crossref","first-page":"bio050385","DOI":"10.1242\/bio.050385","volume":"9","author":"Pirovich","year":"2020","journal-title":"Biology Open"},{"key":"R36","doi-asserted-by":"crossref","first-page":"1900103","DOI":"10.1002\/bies.201900103","volume":"41","author":"Pirovich","year":"2019","journal-title":"BioEssays"},{"key":"R37","doi-asserted-by":"crossref","first-page":"37537","DOI":"10.1074\/jbc.M707280200","volume":"282","author":"Poltermann","year":"2007","journal-title":"Journal of Biological Chemistry"},{"key":"R38","doi-asserted-by":"crossref","first-page":"e1455","DOI":"10.1371\/journal.pntd.0001455","volume":"6","author":"Protasio","year":"2012","journal-title":"PLOS Neglected Tropical Diseases"},{"key":"R39","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.exppara.2006.07.003","volume":"115","author":"Ramajo-Hern\u00e1ndez","year":"2007","journal-title":"Experimental Parasitology"},{"key":"R40","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.molbiopara.2007.08.002","volume":"156","author":"Raverdy","year":"2007","journal-title":"Molecular and Biochemical Parasitology"},{"key":"R41","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1042\/BJ20071097","volume":"409","author":"Rigden","year":"2008","journal-title":"Biochemical Journal"},{"key":"R42","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1038\/s41598-018-21587-4","volume":"8","author":"Samoil","year":"2018","journal-title":"Scientific Reports"},{"key":"R43","doi-asserted-by":"crossref","first-page":"16816","DOI":"10.1038\/s41598-021-96055-7","volume":"11","author":"Silveira","year":"2021","journal-title":"Scientific Reports"},{"key":"R44","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s00436-007-0540-9","volume":"101","author":"Song","year":"2007","journal-title":"Parasitology Research"},{"key":"R45","doi-asserted-by":"crossref","first-page":"12715","DOI":"10.1016\/S0021-9258(18)67150-9","volume":"261","author":"Stankiewicz","year":"1986","journal-title":"Journal of Biological Chemistry"},{"key":"R46","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.2174\/0929867043364603","volume":"11","author":"Stassen","year":"2004","journal-title":"Current Medicinal Chemistry"},{"key":"R47","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S1473-3099(06)70521-7","volume":"6","author":"Steinmann","year":"2006","journal-title":"Lancet Infectious Diseases"},{"key":"R48","doi-asserted-by":"crossref","first-page":"178","DOI":"10.4103\/aja.aja_57_17","volume":"20","author":"Wen","year":"2018","journal-title":"Asian Journal of Andrology"},{"key":"R49","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1126\/science.abb7709","volume":"369","author":"Wendt","year":"2020","journal-title":"Science"},{"issue":"13\u201314","key":"R50","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.ijpara.2021.11.002","volume":"51","author":"Wilson","year":"2021","journal-title":"International Journal for Parasitology"},{"key":"R51","first-page":"121","volume":"293","author":"Winn","year":"1981","journal-title":"Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences"},{"key":"R52","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1007\/s12275-014-4311-x","volume":"52","author":"Zhang","year":"2014","journal-title":"Journal of Microbiology"},{"key":"R53","doi-asserted-by":"crossref","first-page":"4509","DOI":"10.1038\/s41467-020-18234-w","volume":"11","author":"Zhang","year":"2020","journal-title":"Nature Communications"}],"container-title":["Parasite"],"original-title":[],"link":[{"URL":"https:\/\/www.parasite-journal.org\/10.1051\/parasite\/2022042\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T08:27:30Z","timestamp":1662712050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.parasite-journal.org\/10.1051\/parasite\/2022042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022]]},"references-count":53,"alternative-id":["parasite220040"],"URL":"https:\/\/doi.org\/10.1051\/parasite\/2022042","relation":{},"ISSN":["1776-1042"],"issn-type":[{"value":"1776-1042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022]]}}}