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A new paraprobiotic-based treatment for control of Haemonchus contortus in sheep

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dc.contributor.authorSanders, Johnen
dc.contributor.authorXie, Yueen
dc.contributor.authorGazzola, Daviden
dc.contributor.authorLi, Hanchenen
dc.contributor.authorAbraham, Ambilyen
dc.contributor.authorFlanagan, Kellyen
dc.contributor.authorRus, Florentinaen
dc.contributor.authorMiller, Melanieen
dc.contributor.authorHu, Yanen
dc.contributor.authorGuynn, Sierraen
dc.contributor.authorDraper, Austinen
dc.contributor.authorVakalapudi, Sridharen
dc.contributor.authorPetersson, Katherine H.en
dc.contributor.authorZarlenga, Danteen
dc.contributor.authorLi, Robert W.en
dc.contributor.authorUrban, Joseph F., Jr.en
dc.contributor.authorOstroff, Gary R.en
dc.contributor.authorZajac, Anne M.en
dc.contributor.authorAroian, Raffi, Ven
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.contributor.departmentLarge Animal Clinical Sciencesen
dc.date.accessioned2021-03-04T18:37:13Zen
dc.date.available2021-03-04T18:37:13Zen
dc.date.issued2020-12en
dc.description.abstractHaemonchus contortus is a critical parasite of goats and sheep. Infection by this blood-feeding gastrointestinal nematode (GIN) parasite has significant health consequences, especially in lambs and kids. The parasite has developed resistance to virtually all known classes of small molecule anthelmintics used to treat it, giving rise in some areas to multidrug resistant parasites that are very difficult to control. Thus, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt) crystal protein 5B (Cry5B), a naturally occurring protein made by a bacterium widely and safely used around the world as a bioinsecticide, represents a new non-small molecule modality for treating GINs. Cry5B has demonstrated anthelmintic activities against parasites of monogastric animals, including some related to those that infect humans, but has not yet been studied in a ruminant. Here we show that H. contortus adults are susceptible to Cry5B protein in vitro. Cry5B produced in its natural form as a sporecrystal lysate against H. contortus infections in goats had no significant efficacy. However, a new Active Pharmaceutical Ingredient (API) paraprobiotic form of Cry5B called IBaCC (Inactivated Bacterium with Cytosolic Crystals), in which Cry5B crystals are encapsulated in dead Bt cell wall ghosts, showed excellent efficacy in vitro against larval stages of H. contortus and relative protein stability in bovine rumen fluid. When given to sheep experimentally infected with H. contortus as three 60 mg/kg doses, Cry5B IBaCC resulted in significant reductions in fecal egg counts (90%) and parasite burdens (72%), with a very high impact on female parasites (96% reduction). These data indicate that Cry5B IBaCC is a potent new treatment tool for small ruminants in the battle against H. contortus.en
dc.description.adminPublic domain – authored by a U.S. government employeeen
dc.description.notesThis project was supported by (1) the National Institutes of Health/National Institute of Allergy and Infectious Diseases grants R01A1056189 and R01A150866 to R.V.A., (2) Agriculture and Food Research Initiative Competitive Grantno. 2015-11323 from the USDA National Institute of Food and Agriculture to R.V.A.en
dc.description.sponsorshipNational Institutes of Health/National Institute of Allergy and Infectious DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01A1056189, R01A150866]; Agriculture and Food Research Initiative Competitive Grant from the USDA National Institute of Food and Agriculture [2015-11323]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.ijpddr.2020.11.004en
dc.identifier.issn2211-3207en
dc.identifier.pmid33242790en
dc.identifier.urihttp://hdl.handle.net/10919/102613en
dc.identifier.volume14en
dc.language.isoenen
dc.rightsPublic Domainen
dc.rights.urihttp://creativecommons.org/publicdomain/mark/1.0/en
dc.subjectHaemonchus contortusen
dc.subjectAnthelminticen
dc.subjectBacillus thuringiensis crystal Protein Cry5Ben
dc.subjectParaprobioticen
dc.subjectInactivated bacterium with cytosolic crystal (IBaCC)en
dc.subjectSheepen
dc.titleA new paraprobiotic-based treatment for control of Haemonchus contortus in sheepen
dc.title.serialInternational Journal for Parasitology-Drugs and Drug Resistanceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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