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We have reengineered OXA to be effective against S. haematobium and S. japonicum. Three derivatives stand out, CIDD-0066790, CIDD-0072229, and CIDD-0149830 as they kill all three major human schistosome species. However, questions remain. Is the OXA mode of action conserved in derivatives? RNA-interference experiments demonstrate that knockdown of the SmSULT, ShSULT, and SjSULT results in resistance to CIDD-0066790. Confirming that the OXA-derivative mode of action is conserved. Next is the level of expression of the schistosome SULTs in each species, as well as changes in SULT expression throughout development in S. mansoni. Using multiple tools, our data show that SmSULT has higher expression compared to ShSULT and SjSULT. Third, is the localization of SULT in the adult, multicellular eucaryotic schistosome species. We utilized fluorescence in situ hybridization and uptake of radiolabeled OXA to determine that multiple cell types throughout the adult schistosome worm express SULT. Thus, we hypothesize the ability of many cells to express the sulfotransferase accounts for the ability of the OXA derivatives to kill adult worms. Our studies demonstrate that the OXA derivatives are able to kill all three human schistosome species and thus will be a useful complement to PZQ.<\/jats:p>","DOI":"10.3390\/pharmaceutics14071416","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T05:41:06Z","timestamp":1657086066000},"page":"1416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Schistosome Sulfotransferases: Mode of Action, Expression and Localization"],"prefix":"10.3390","volume":"14","author":[{"given":"Meghan A.","family":"Guzman","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Health, San Antonio, TX 78229, USA"},{"name":"Department of Biochemistry and Structural Biology, University of Texas Health, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia","family":"Rugel","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Health, San Antonio, TX 78229, USA"},{"name":"Department of Biochemistry and Structural Biology, University of Texas Health, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8701-4859","authenticated-orcid":false,"given":"Sevan N.","family":"Alwan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Structural Biology, University of Texas Health, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reid","family":"Tarpley","sequence":"additional","affiliation":[{"name":"Center for Innovative Drug Discovery, University of Texas at San Antonio, San Antonio, TX 78249, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3517-6033","authenticated-orcid":false,"given":"Alexander B.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Structural Biology, University of Texas Health, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2611-8106","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric D.","family":"Chevalier","sequence":"additional","affiliation":[{"name":"Host Pathogen Interactions Program, Texas Biomedical Research Institute, San Antonio, TX 78227, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George R.","family":"Wendt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"James J.","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J. C.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Disease Intervention & Prevention, Texas Biomedical Research Institute, San Antonio, TX 78227, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanton F.","family":"McHardy","sequence":"additional","affiliation":[{"name":"Center for Innovative Drug Discovery, University of Texas at San Antonio, San Antonio, TX 78249, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip T.","family":"LoVerde","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Structural Biology, University of Texas Health, San Antonio, TX 78229, USA"},{"name":"Department of Pathology and Laboratory Medicine, University of Texas Health, San Antonio, TX 78229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.2174\/1389557511313040003","article-title":"The evolution of drugs on schistosoma treatment: Looking to the past to improve the future","volume":"13","author":"Galdino","year":"2013","journal-title":"Mini Rev. 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