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一种表达Cry5B的灭活细菌(副益生菌),用作治疗大型动物的 和 属感染的药物。

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

作者信息

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, Aroian Raffi V

机构信息

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.

出版信息

One Health. 2021 Mar 26;12:100241. doi: 10.1016/j.onehlt.2021.100241. eCollection 2021 Jun.

DOI:10.1016/j.onehlt.2021.100241
PMID:33889707
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8048022/
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.

摘要

蛔虫和类圆线虫是蛔科中的重要寄生虫,它们是大型的、广泛存在的肠道寄生线虫,感染所有脊椎动物类别。在兽医学中,寄生线虫的耐药性以及在人类医学中药物的顽固性在全球范围内都在增加,几乎没有新的治疗类别出现。其中一些寄生虫是人畜共患病原体,例如猪蛔虫会从人类传播到猪身上,而粪类圆线虫会从人类传播到马身上。开发针对这类寄生虫的新疗法将对人类和牲畜健康产生重大影响。在这里,我们测试了一种表达具有已知驱虫特性的Cry5B蛋白的副益生菌或死益生菌对人畜共患病原体猪蛔虫和粪类圆线虫的治疗能力。这种被称为IBaCC的副益生菌使猪蛔虫幼虫中毒,并在一种针对该寄生虫的新小鼠模型中对肠道猪蛔虫感染非常有效。发酵规模扩大到350升以治疗猪和马。单剂量的Cry5B IBaCC几乎完全清除了猪体内的猪蛔虫感染。此外,单剂量的Cry5B IBaCC使感染粪类圆线虫的马驹粪便中的虫卵计数降至零,显示出至少与目前用于对抗这种寄生虫的驱虫药效果相当,甚至可能更优。因此,Cry5B IBaCC代表了一种针对蛔科的新的、副益生菌的“同一健康”方法,它安全、有效、可大规模扩展、稳定,并且在世界发达和发展中地区的人类和兽医学中都有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/8048022/1521195fd8dd/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/8048022/f6c81e970eab/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/8048022/5a3a237b25df/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/8048022/1ed79b775d53/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/8048022/6238e53051f6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/8048022/1521195fd8dd/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/8048022/f6c81e970eab/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/8048022/5a3a237b25df/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/8048022/1ed79b775d53/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/8048022/6238e53051f6/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afb5/8048022/1521195fd8dd/gr4.jpg

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