{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:34:46Z","timestamp":1792211686647,"version":"4.4.0"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>On entering the mammalian host, schistosomes transition from a freshwater environment where resources are scarce, to an environment where there is an unlimited supply of glucose, their preferred energy substrate. Adult schistosome glycolytic activity consumes almost five times the parasite\u2019s dry weight in glucose per day to meet the parasite\u2019s energy demands, and the schistosome glycolytic enzymes and mechanisms for glucose uptake that sustain this metabolic activity have previously been identified. However, little is known of the parasite processes that regulate schistosome glucose metabolism. We previously described the <jats:italic>Schistosoma mansoni<\/jats:italic> ortholog of 5\u2032 AMP-Activated Protein Kinase (AMPK), which is a central regulator of energy metabolism in eukaryotes, and characterized the developmental regulation of its expression and activity in <jats:italic>S. mansoni<\/jats:italic>. Here we sought to explore the function of AMPK in schistosomes and test whether it regulates parasite glycolysis. Adult schistosomes mounted a compensatory response to chemical inhibition of AMPK \u03b1, resulting in increased AMPK \u03b1 protein abundance and activity. RNAi inhibition of AMPK \u03b1 expression, however, suggests that AMPK \u03b1 is not required for adult schistosome viability <jats:italic>in vitro<\/jats:italic>. Larval schistosomula, on the other hand, are sensitive to chemical AMPK \u03b1 inhibition, and this correlates with inactivity of the AMPK \u03b1 gene in this life cycle stage that precludes a compensatory response to AMPK inhibition. While our data indicate that AMPK is not essential in adult schistosomes, our results suggest that AMPK regulates adult worm glycogen stores, influencing both glycogen utilization and synthesis. AMPK may therefore play a role in the ability of adult schistosomes to survive <jats:italic>in vivo<\/jats:italic> stressors such as transient glucose deprivation and oxidative stress. These findings suggest that AMPK warrants further investigation as a potential drug target, especially for interventions aimed at preventing establishment of a schistosome infection.<\/jats:p>","DOI":"10.3389\/fmicb.2021.726465","type":"journal-article","created":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T01:23:12Z","timestamp":1630718592000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Schistosome AMPK Is Required for Larval Viability and Regulates Glycogen Metabolism in Adult Parasites"],"prefix":"10.3389","volume":"12","author":[{"given":"Kasandra S.","family":"Hunter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Mentink-Kane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1051\/parasite\/2008154573","article-title":"Insulin receptors and glucose uptake in the human parasite Schistosoma mansoni.","volume":"15","author":"Ahier","year":"2008","journal-title":"Parasite"},{"key":"B2","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1042\/bj20070797","article-title":"The selectivity of protein kinase inhibitors: a further update.","volume":"408","author":"Bain","year":"2007","journal-title":"Biochem. 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