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A new paraprobiotic-based treatment for control of Haemonchus contortus in sheep
International Journal for Parasitology: Drugs and Drug Resistance ( IF 4 ) Pub Date : 2020-11-19 , DOI: 10.1016/j.ijpddr.2020.11.004
John Sanders 1 , Yue Xie 2 , David Gazzola 3 , Hanchen Li 3 , Ambily Abraham 3 , Kelly Flanagan 3 , Florentina Rus 3 , Melanie Miller 4 , Yan Hu 5 , Sierra Guynn 6 , Austin Draper 7 , Sridhar Vakalapudi 7 , Katherine H Petersson 8 , Dante Zarlenga 9 , Robert W Li 9 , Joseph F Urban 10 , Gary R Ostroff 3 , Anne Zajac 1 , Raffi V Aroian 3
Affiliation  

Haemonchus contortus is a critical parasite of goats and sheep. Infection by this blood-feeding gastrointestinal nematode (GIN) parasite has significant health consequences, especially in lambs and kids. The parasite has developed resistance to virtually all known classes of small molecule anthelmintics used to treat it, giving rise in some areas to multidrug resistant parasites that are very difficult to control. Thus, new anthelmintics are urgently needed. Bacillus thuringiensis (Bt) crystal protein 5B (Cry5B), a naturally occurring protein made by a bacterium widely and safely used around the world as a bioinsecticide, represents a new non-small molecule modality for treating GINs. Cry5B has demonstrated anthelmintic activities against parasites of monogastric animals, including some related to those that infect humans, but has not yet been studied in a ruminant. Here we show that H. contortus adults are susceptible to Cry5B protein in vitro. Cry5B produced in its natural form as a spore-crystal lysate against H. contortus infections in goats had no significant efficacy. However, a new Active Pharmaceutical Ingredient (API) paraprobiotic form of Cry5B called IBaCC (Inactivated Bacterium with Cytosolic Crystals), in which Cry5B crystals are encapsulated in dead Bt cell wall ghosts, showed excellent efficacy in vitro against larval stages of H. contortus and relative protein stability in bovine rumen fluid. When given to sheep experimentally infected with H. contortus as three 60 mg/kg doses, Cry5B IBaCC resulted in significant reductions in fecal egg counts (90%) and parasite burdens (72%), with a very high impact on female parasites (96% reduction). These data indicate that Cry5B IBaCC is a potent new treatment tool for small ruminants in the battle against H. contortus.



中文翻译:

一种新的基于副益生菌的治疗方法,用于控制绵羊扭曲血霉病

Haemonchus contortus是山羊和绵羊的重要寄生虫。这种吸血性胃肠道线虫 (GIN) 寄生虫感染会对健康产生重大影响,尤其是对羔羊和儿童。这种寄生虫已经对几乎所有已知种类的用于治疗它的小分子驱虫药产生了抗药性,从而在某些地区产生了非常难以控制的多重耐药性寄生虫。因此,迫切需要新的驱虫剂。苏云金芽孢杆菌(Bt) 晶体蛋白 5B (Cry5B) 是一种由细菌制成的天然蛋白质,在世界范围内广泛且安全地用作生物杀虫剂,代表了一种用于治疗 GIN 的新型非小分子方式。Cry5B 已证明对单胃动物的寄生虫具有驱虫活性,包括一些与感染人类相关的寄生虫,但尚未在反刍动物中进行研究。在这里,我们表明,捻转血矛线虫成虫易受Cry5B蛋白在体外。Cry5B 以其天然形式作为孢子晶体裂解物产生,以抵抗H. contortus山羊感染没有显着疗效。然而,Cry5B 的一种新的活性药物成分 (API) 副益生菌形式称为 IBaCC(具有胞质晶体的灭活细菌),其中 Cry5B 晶体被封装在死 Bt 细胞壁幽灵中,在体外H. contortus和牛瘤胃液中蛋白质的相对稳定性。当给予羊实验感染捻转血矛线虫三个60mg / kg的剂量下,Cry5B IBaCC导致粪便卵数(90%)和寄生虫的负担(72%),对女性寄生虫非常高的抗冲击显著减少(96 % 减少)。这些数据表明,Cry5B IBaCC 是一种有效的新型小反刍动物治疗工具。H. 扭曲

更新日期:2020-11-23
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