{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T23:41:13Z","timestamp":1787787673504,"version":"build-2784847793"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009828","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000}}],"reference-count":126,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["107475\/Z\/15\/Z"],"award-info":[{"award-number":["107475\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["HHSN272201000005I"],"award-info":[{"award-number":["HHSN272201000005I"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"David & Eleanor James"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    \u03b1-galactosidase (\u03b1-GAL) and \u03b1-N-acetylgalactosaminidase (\u03b1-NAGAL) are two glycosyl hydrolases responsible for maintaining cellular homeostasis by regulating glycan substrates on proteins and lipids. Mutations in the human genes encoding either enzyme lead to neurological and neuromuscular impairments seen in both Fabry- and Schindler\/Kanzaki- diseases. Here, we investigate whether the parasitic blood fluke\n                    <jats:italic>Schistosoma mansoni<\/jats:italic>\n                    , responsible for the neglected tropical disease schistosomiasis, also contains functionally important \u03b1-GAL and \u03b1-NAGAL proteins. As infection, parasite maturation and host interactions are all governed by carefully-regulated glycosylation processes, inhibiting\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>mansoni\u2019<\/jats:italic>\n                    s \u03b1-GAL and \u03b1-NAGAL activities could lead to the development of novel chemotherapeutics. Sequence and phylogenetic analyses of putative \u03b1-GAL\/\u03b1-NAGAL protein types showed Smp_089290 to be the only\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>mansoni<\/jats:italic>\n                    protein to contain the functional amino acid residues necessary for \u03b1-GAL\/\u03b1-NAGAL substrate cleavage. Both \u03b1-GAL and \u03b1-NAGAL enzymatic activities were higher in females compared to males (\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.05; \u03b1-NAGAL &gt; \u03b1-GAL), which was consistent with\n                    <jats:italic>smp_089290<\/jats:italic>\n                    \u2019s female biased expression. Spatial localisation of\n                    <jats:italic>smp_089290<\/jats:italic>\n                    revealed accumulation in parenchymal cells, neuronal cells, and the vitellaria and mature vitellocytes of the adult schistosome. siRNA-mediated knockdown (&gt;90%) of\n                    <jats:italic>smp_089290<\/jats:italic>\n                    in adult worms significantly inhibited \u03b1-NAGAL activity when compared to control worms (\n                    <jats:italic>siLuc<\/jats:italic>\n                    treated males,\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.01;\n                    <jats:italic>siLuc<\/jats:italic>\n                    treated females,\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.05). No significant reductions in \u03b1-GAL activities were observed in the same extracts. Despite this, decreases in \u03b1-NAGAL activities correlated with a significant inhibition in adult worm motility as well as in egg production. Programmed CRISPR\/Cas9 editing of\n                    <jats:italic>smp_089290<\/jats:italic>\n                    in adult worms confirmed the egg reduction phenotype. Based on these results, Smp_089290 was determined to act predominantly as an \u03b1-NAGAL (hereafter termed SmNAGAL) in schistosome parasites where it participates in coordinating movement and oviposition processes. Further characterisation of SmNAGAL and other functionally important glycosyl hydrolases may lead to the development of a novel anthelmintic class of compounds.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009828","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T14:30:52Z","timestamp":1642084252000},"page":"e1009828","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["Schistosoma mansoni \u03b1-N-acetylgalactosaminidase (SmNAGAL) regulates coordinated parasite movement and egg production"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5638-6323","authenticated-orcid":true,"given":"Benjamin J.","family":"Hulme","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7537-8663","authenticated-orcid":true,"given":"Kathrin K.","family":"Geyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine E.","family":"Forde-Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda","family":"Padalino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9139-5727","authenticated-orcid":true,"given":"Dylan W.","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9411-8883","authenticated-orcid":true,"given":"Wannaporn","family":"Ittiprasert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2079-0973","authenticated-orcid":true,"given":"Shannon E.","family":"Karinshak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria H.","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8674-1181","authenticated-orcid":true,"given":"Iain W.","family":"Chalmers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1765-0002","authenticated-orcid":true,"given":"Paul J.","family":"Brindley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3545-7804","authenticated-orcid":true,"given":"Cornelis H.","family":"Hokke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3932-5502","authenticated-orcid":true,"given":"Karl F.","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"issue":"1","key":"ppat.1009828.ref001","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-018-0013-8","article-title":"Schistosomiasis","volume":"4","author":"DP McManus","year":"2018","journal-title":"Nat Rev Dis Primers"},{"issue":"31","key":"ppat.1009828.ref002","doi-asserted-by":"crossref","first-page":"7936","DOI":"10.1002\/anie.201208390","article-title":"Schistosomiasis chemotherapy","volume":"52","author":"SA Thetiot-Laurent","year":"2013","journal-title":"Angew Chem Int Ed Engl"},{"issue":"2","key":"ppat.1009828.ref003","doi-asserted-by":"crossref","first-page":"307","DOI":"10.4269\/ajtmh.1998.59.307","article-title":"Studies on schistosomiasis in western Kenya: II. 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