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.
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This project was supported by (1) the National Institutes of Health/National Institute of Allergy and Infectious Diseases grants R01AI056189 and R01AI50866 to R.V.A., (2) Agriculture and Food Research Initiative Competitive Grant no. 2015–11323 from the USDA National Institute of Food and Agriculture to R.V.A., and (3) CRIS project #8042–31000-107-00D: “Molecular Approaches to Control Intestinal Parasites that Affect the Microbiome in Swine and Small Ruminants” to J.F.U.
Urban, Joseph F.; Nielsen, Martin K.; Gazzola, David; Xie, Yue; Beshah, Ethiopia; Hu, Yan; Li, Hanchen; Rus, Florentina; Flanagan, Kelly; Draper, Austin; Vakalapudi, Sridhar; Li, Robert W.; Ostroff, Gary R.; and Aroian, Raffi V., "An Inactivated Bacterium (Paraprobiotic) Expressing Bacillus thuringiensis Cry5B as a Therapeutic for Ascaris and Parascaris spp. Infections in Large Animals" (2021). Maxwell H. Gluck Equine Research Center Faculty Publications. 56.