UMMS Affiliation

Program in Molecular Medicine

Publication Date

2020-12-01

Document Type

Article

Disciplines

Parasitology | Veterinary Medicine

Abstract

Haemonchus 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 spore-crystal 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.

Keywords

Anthelmintic, Bacillus thuringiensis crystal Protein Cry5B, Haemonchus contortus, Inactivated bacterium with cytosolic crystal (IBaCC), Paraprobiotic, Sheep

Rights and Permissions

© 2020 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/.

DOI of Published Version

10.1016/j.ijpddr.2020.11.004

Source

Sanders J, Xie Y, Gazzola D, Li H, Abraham A, Flanagan K, Rus F, Miller M, Hu Y, Guynn S, Draper A, Vakalapudi S, Petersson KH, Zarlenga D, Li RW, Urban JF Jr, Ostroff GR, Zajac A, Aroian RV. A new paraprobiotic-based treatment for control of Haemonchus contortus in sheep. Int J Parasitol Drugs Drug Resist. 2020 Dec;14:230-236. doi: 10.1016/j.ijpddr.2020.11.004. Epub 2020 Nov 19. PMID: 33242790; PMCID: PMC7695930. Link to article on publisher's site

Journal/Book/Conference Title

International journal for parasitology. Drugs and drug resistance

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

33242790

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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