{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T05:22:14Z","timestamp":1762406534696,"version":"build-2065373602"},"reference-count":79,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R21AI177019","R01 AI154777","R21AI182705","R01AI179768"],"award-info":[{"award-number":["R21AI177019","R01 AI154777","R21AI182705","R01AI179768"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011820","name":"Saudi Arabian Cultural Mission","doi-asserted-by":"crossref","award":["FG-1497532"],"award-info":[{"award-number":["FG-1497532"]}],"id":[{"id":"10.13039\/501100011820","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Cryptosporidium is a waterborne gastrointestinal parasite that causes diarrheal disease worldwide. Currently, there are no effective therapeutics to treat cryptosporidiosis. Since natural products are a known source of anti-parasitic compounds, we screened a library of extracts and pure compounds isolated from bacteria and fungi collected from subterranean environments for anti-Cryptosporidium activity. Seven norditerpene lactones isolated from the fungus Oidiodendron truncatum collected from the Soudan Iron mine in Minnesota showed potent activity and were further tested to identify the most active compounds. The availability of a diverse suite of natural structural analogs with varying activities allowed us to determine some structure\u2013activity relationships for both anti-parasitic activity and cytotoxicity. The two most potent compounds, oidiolactones A and B, had EC50s against C. parvum of 530 and 240 nM, respectively, without cytotoxicity to host cells. Both compounds also inhibited the related parasite Toxoplasma gondii. Oidiolactone A was active against asexual, but not sexual, stages of C. parvum, and killed parasites within 8 h of treatment. This compound reduced C. parvum infection by 70% in IFN\u03b3\u2212\/\u2212 mice, with no signs of toxicity. The high potency, low cytotoxicity, and in vivo activity combined with high production and synthetic accessibility make these oidiolactones attractive scaffolds for the development of new anti-Cryptosporidium therapeutics.<\/jats:p>","DOI":"10.3390\/microorganisms13112527","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:11:16Z","timestamp":1762254676000},"page":"2527","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Norditerpene Natural Products from Subterranean Fungi with Anti-Parasitic Activity"],"prefix":"10.3390","volume":"13","author":[{"given":"Alexandra","family":"Kolas","sequence":"first","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yudi","family":"Rusman","sequence":"additional","affiliation":[{"name":"Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9455-2919","authenticated-orcid":false,"given":"Ana C. 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G.","family":"Maia","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica M.","family":"Williams","sequence":"additional","affiliation":[{"name":"Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6148-5203","authenticated-orcid":false,"given":"Jiashu","family":"Xie","sequence":"additional","affiliation":[{"name":"Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1374-0828","authenticated-orcid":false,"given":"Roshan","family":"Katekar","sequence":"additional","affiliation":[{"name":"Center for Drug Design, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4561-9005","authenticated-orcid":false,"given":"Fernanda G.","family":"Fumuso","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0335-2207","authenticated-orcid":false,"given":"Alexis","family":"Cotto-Rosario","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chidiebere N.","family":"Onoh","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanen","family":"Baggar","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary L.","family":"Piaskowski","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Baigorria","sequence":"additional","affiliation":[{"name":"Division of Molecular Microbiology, Burnett School of Biomedical Sciences, University of Central Florida, 12722 Research Parkway, Orlando, FL 32826, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6146-5309","authenticated-orcid":false,"given":"Raphaella","family":"Paes","sequence":"additional","affiliation":[{"name":"Division of Molecular Microbiology, Burnett School of Biomedical Sciences, University of Central Florida, 12722 Research Parkway, Orlando, FL 32826, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debopam","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Division of Molecular Microbiology, Burnett School of Biomedical Sciences, University of Central Florida, 12722 Research Parkway, Orlando, FL 32826, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyssa J.","family":"Weible","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2007-2170","authenticated-orcid":false,"given":"Kayode K.","family":"Ojo","sequence":"additional","affiliation":[{"name":"Center for Emerging and Reemerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA 98109, USA"},{"name":"Department of Global Health, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2757-754X","authenticated-orcid":false,"given":"Roberta M.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4976-598X","authenticated-orcid":false,"given":"Christine 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