UMMS Affiliation

Program in Molecular Medicine

Publication Date

2021-03-26

Document Type

Article

Disciplines

Immunology and Infectious Disease | Parasitic Diseases | Veterinary Medicine

Abstract

Ascaris and Parascaris are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon. Some of these parasites are zoonotic, e.g., Ascaris is passed from humans to pigs and vice versa. The development of new therapies against this family of parasites would have major implications for both human and livestock health. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the Bacillus thuringiensis Cry5B protein with known anthelmintic properties, against zoonotic Ascaris suum and Parascaris spp. This paraprobiotic, known as IBaCC, intoxicated A. suum larvae in vitro and was highly effective in vivo against intestinal A. suum infections in a new mouse model for this parasite. Fermentation was scaled up to 350 l to treat pigs and horses. Single dose Cry5B IBaCC nearly completely cleared A. suum infections in pigs. Furthermore, single dose Cry5B IBaCC drove fecal egg counts in Parascaris-infected foals to zero, showing at least parity with, and potential superiority to, current efficacy of anthelmintics used against this parasite. Cry5B IBaCC therefore represents a new, paraprobiotic One Health approach towards targeting Ascarididae that is safe, effective, massively scalable, stable, and useful in human and veterinary medicine in both the developed and developing regions of the world.

Keywords

Anthelmintic, Ascaris, Bacillus thuringiensis, Cry5B crystal protein, Paraprobiotic, Parascaris

Rights and Permissions

Copyright © 2021 The Author(s). 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.onehlt.2021.100241

Source

Urban JF Jr, Nielsen MK, Gazzola D, Xie Y, Beshah E, Hu Y, Li H, Rus F, Flanagan K, Draper A, Vakalapudi S, Li RW, Ostroff GR, Aroian RV. An inactivated bacterium (paraprobiotic) expressing Bacillus thuringiensis Cry5B as a therapeutic for Ascaris and Parascaris spp. infections in large animals. One Health. 2021 Mar 26;12:100241. doi: 10.1016/j.onehlt.2021.100241. PMID: 33889707; PMCID: PMC8048022. Link to article on publisher's site

Journal/Book/Conference Title

One health (Amsterdam, Netherlands)

Related Resources

Link to Article in PubMed

PubMed ID

33889707

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.

Share

COinS