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One health (Amsterdam, Netherlands)2021; 12; 100241; doi: 10.1016/j.onehlt.2021.100241

An inactivated bacterium (paraprobiotic) expressing Bacillus thuringiensis Cry5B as a therapeutic for Ascaris and Parascaris spp. infections in large animals.

Abstract: and 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, , is passed from humans to pigs and . 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 Cry5B protein with known anthelmintic properties, against zoonotic and spp. This paraprobiotic, known as IBaCC, intoxicated larvae and was highly effective against intestinal 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 infections in pigs. Furthermore, single dose Cry5B IBaCC drove fecal egg counts in -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.
© 2021 The Author(s).
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Publication Date: 2021-03-26 PubMed ID: 33889707PubMed Central: PMC8048022DOI: 10.1016/j.onehlt.2021.100241Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explores the use of a paraprobiotic (an inactivated bacterium) that produces Cry5B protein for treating Ascaris and Parascaris spp. infections in large animals. The effectiveness of this new treatment is demonstrated in pigs and horses, offering an alternative approach to combat parasitic nematode resistance.

Scope of the Research

  • The research is focused on developing an effective treatment for Ascaris and Parascaris spp., two of the parasitic nematodes identified in the Ascarididae family that infect vertebrates.
  • These parasites can cause substantial harm to human and livestock health. Moreover, some species can transmit from human to livestock and vice versa, making them zoonotic.
  • A significant concern that makes the development of a new treatment necessary is the increasing resistance these parasites have towards the existing drugs, both in human and veterinary medicine.

The Proposed Solution

  • The proposed solution is the use of an inactivated bacterium known as a paraprobiotic, specifically IBaCC, that expresses the Cry5B protein with anthelmintic or deworming properties.
  • The effectiveness of the paraprobiotic was measured based on its ability to intoxicate Ascaris larvae and its effect against intestinal Ascaris infections in a new mouse model.

Results of the Study

  • Successful scale-up fermentation to 350 liters was achieved, enabling the treatment of larger animals such as pigs and horses.
  • The research shows that a single dose of Cry5B IBaCC could almost completely eradicate Ascaris infections in pigs.
  • Similarly, the Cry5B IBaCC treatment for horses infected with Parascaris spp. drove fecal egg counts to zero, showing its potential to surpass or at least match current anthelmintic effectiveness.

Conclusion of the Study

  • The study concludes that Cry5B IBaCC represents an innovative paraprobiotic One Health approach towards combating Ascarididae.
  • The treatment is marked as safe and effective, with the ability to be massively scalable and stable.
  • Its use in both human and veterinary medicine and its applicability across both developed and developing regions of the world enhances its value.

Cite This Article

APA
Urban JF, 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. (2021). An inactivated bacterium (paraprobiotic) expressing Bacillus thuringiensis Cry5B as a therapeutic for Ascaris and Parascaris spp. infections in large animals. One Health, 12, 100241. https://doi.org/10.1016/j.onehlt.2021.100241

Publication

One health (Amsterdam, Netherlands)
ISSN: 2352-7714
NlmUniqueID: 101660501
Country: Netherlands
Language: English
Volume: 12
Pages: 100241
PII: 100241

Researcher Affiliations

Urban, Joseph F
  • U. S. Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal and Parasitic Diseases Laboratory, Beltsville, MD, United States of America.
  • U. S. Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics and Immunology Laboratory, Beltsville, MD, United States of America.
Nielsen, Martin K
  • M.H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, United States of America.
Gazzola, David
  • Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America.
Xie, Yue
  • U. S. Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal and Parasitic Diseases Laboratory, Beltsville, MD, United States of America.
  • U. S. Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics and Immunology Laboratory, Beltsville, MD, United States of America.
  • Department of Parasitology, College of Veterinary Medicine, Sichuan Agricultural University, Sichuan, China.
Beshah, Ethiopia
  • U. S. Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal and Parasitic Diseases Laboratory, Beltsville, MD, United States of America.
  • U. S. Department of Agriculture, Agricultural Research Service, Beltsville Human Nutrition Research Center, Diet, Genomics and Immunology Laboratory, Beltsville, MD, United States of America.
Hu, Yan
  • Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America.
Li, Hanchen
  • Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America.
Rus, Florentina
  • Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America.
Flanagan, Kelly
  • Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America.
Draper, Austin
  • Synthetic Biomanufacturing Facility, Utah State University, Logan, UT, United States of America.
Vakalapudi, Sridhar
  • Synthetic Biomanufacturing Facility, Utah State University, Logan, UT, United States of America.
Li, Robert W
  • U. S. Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal and Parasitic Diseases Laboratory, Beltsville, MD, United States of America.
Ostroff, Gary R
  • Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America.
Aroian, Raffi V
  • Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America.

Grant Funding

  • R01 AI056189 / NIAID NIH HHS
  • R01 AI150866 / NIAID NIH HHS

Conflict of Interest Statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Citations

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