{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:32:46Z","timestamp":1792459966677,"version":"4.5.0"},"reference-count":71,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000199","name":"USDA In-House Appropriated funds","doi-asserted-by":"publisher","award":["8042-32000-116-000-D"],"award-info":[{"award-number":["8042-32000-116-000-D"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"USDA In-House Appropriated funds","doi-asserted-by":"publisher","award":["5030-3200-223-00D"],"award-info":[{"award-number":["5030-3200-223-00D"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["R01HD099072-05"],"award-info":[{"award-number":["R01HD099072-05"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Haemonchus contortus is a blood-feeding gastrointestinal nematode that significantly impacts the health and productivity of small ruminants. The burden of parasitism and the escalating incidence of anthelmintic resistance necessitate alternative control methods. Here, we characterize the enzymatic activities of five mammalian cell-expressed recombinant H. contortus cysteine proteases (HcCPs), which include two cathepsin B-like proteins (HcCBP1 and HcCBP2) and three cysteine protease 1 proteins (HcCP1a, HcCP1b, and HcCP1c). We hypothesize that these enzymes degrade host blood proteins, thereby facilitating the parasite\u2019s nutrient acquisition and survival. Using synthetic cathepsin (cat) substrates, we show that HcCBP2 was the only protein that exhibited high catB\/L but low catB or catK activity, which was inhibited by the cysteine protease inhibitor E-64. All mHcCPs degraded fibrinogen (Fg), which led to delayed plasma clotting, reduced clot density, and lysed plasma clots. All HcCPs partially degraded hemoglobin (Hb), except for mHcCBP2, which degraded Hb and bovine serum albumin completely and bovine IgG partially in the presence of a reducing agent. In conclusion, by sustaining blood feeding and facilitating immune evasion and nutrient acquisition, the HcCPs may play an essential role in the parasite\u2019s survival. Thus, vaccines or cysteine protease inhibitors targeting these parasitic enzymes may mitigate or prevent infections.<\/jats:p>","DOI":"10.3390\/ijms262412077","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T08:46:52Z","timestamp":1765874812000},"page":"12077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Catalytically Active Recombinant Cysteine Proteases of Haemonchus contortus: Their Ability to Degrade Host Blood Proteins and Modulate Coagulation"],"prefix":"10.3390","volume":"26","author":[{"given":"Athira C.","family":"Karunakaran","sequence":"first","affiliation":[{"name":"Animal Parasitic Diseases Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA"},{"name":"Oak Ridge Institute for Science and Education, Oak Ridge, TN 37830, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"Bakshi","sequence":"additional","affiliation":[{"name":"Animal Parasitic Diseases Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA"},{"name":"Department of Veterinary Medicine, University of Maryland, College Park, MD 20740, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4290-7682","authenticated-orcid":false,"given":"Arunraj M.","family":"Rajendrakumar","sequence":"additional","affiliation":[{"name":"Animal Parasitic Diseases Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA"},{"name":"Department of Veterinary Medicine, University of Maryland, College Park, MD 20740, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer H.","family":"Wilson-Welder","sequence":"additional","affiliation":[{"name":"Infectious Bacterial Diseases Research Unit, National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, IA 50010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffi V.","family":"Aroian","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3151-4381","authenticated-orcid":false,"given":"Erich M.","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Jane","family":"Homan","sequence":"additional","affiliation":[{"name":"ioGenetics LLC, Madison, WI 53704, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary R.","family":"Ostroff","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethiopia","family":"Beshah","sequence":"additional","affiliation":[{"name":"Animal Parasitic Diseases Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliseo","family":"Miramontes","sequence":"additional","affiliation":[{"name":"Animal Parasitic Diseases Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne Dias","family":"Papadopoulos","sequence":"additional","affiliation":[{"name":"Animal Parasitic Diseases Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Bowdridge","sequence":"additional","affiliation":[{"name":"Davis College of Agriculture and Natural Resources, Morgantown, WV 26506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dante S.","family":"Zarlenga","sequence":"additional","affiliation":[{"name":"Animal Parasitic Diseases Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland, College Park, MD 20740, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3764-8981","authenticated-orcid":false,"given":"Wenbin","family":"Tuo","sequence":"additional","affiliation":[{"name":"Animal Parasitic Diseases Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD 20705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Adduci, I., Sajovitz, F., Hinney, B., Lichtmannsperger, K., Joachim, A., Wittek, T., and Yan, S. 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