An inactivated bacterium (paraprobiotic) expressing Bacillus thuringiensis Cry5B as a therapeutic for Ascaris and Parascaris spp. infections in large animals
Joseph F. Urban, Jr,
Martin K. Nielsen,
David Gazzola,
Yue Xie,
Ethiopia Beshah,
Yan Hu,
Hanchen Li,
Florentina Rus,
Kelly Flanagan,
Austin Draper,
Sridhar Vakalapudi,
Robert W. Li,
Gary R. Ostroff,
Raffi V. Aroian
Affiliations
Joseph F. Urban, Jr
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; Corresponding author at: U. S. Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal and Parasitic Diseases Laboratory, Beltsville, MD, United States of America.
Martin K. Nielsen
M.H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, United States of America
David Gazzola
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America
Yue Xie
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
Ethiopia Beshah
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
Yan Hu
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America
Hanchen Li
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America
Florentina Rus
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America
Kelly Flanagan
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America
Austin Draper
Synthetic Biomanufacturing Facility, Utah State University, Logan, UT, United States of America
Sridhar Vakalapudi
Synthetic Biomanufacturing Facility, Utah State University, Logan, UT, United States of America
Robert W. Li
U. S. Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal and Parasitic Diseases Laboratory, Beltsville, MD, United States of America
Gary R. Ostroff
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America
Raffi V. Aroian
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America; Corresponding author.
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.
