Milk-derived antimicrobial peptides to protect against Neonatal Diarrheal Disease: An alternative to antibiotics

Heather L. Wilson , Rachelle M. Buchanan , Brenda Allan , Suresh K. Tikoo
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引用次数: 7

Abstract

Neonatal Diarrheal Disease is responsible for significant economic losses to the livestock industries in Canada and around the world. Microbes responsible are diverse and include Escherichia coli, Salmonella, Rotavirus, Coronavirus and Cryptosporidia. While the use of antibiotics as a treatment for bacterial infections and as a prophylactic additive in feed has dramatically improved cattle production in recent decades, the increasing pressure to reduce or eliminate use of antibiotics in animals has caused the livestock industry to seek appropriate alternatives. Antimicrobial/Host Defense Peptides are natural compounds present on skin and in secretions in plants and animals that are microbicidal for bacteria, viruses, and parasites and they stimulate the immune system to combat infectious diseases. Our objective is to establish orally-obtained Host Defense Peptides (HDPs) as an alternative to antibiotics to protect against Neonatal Diarrheal Disease in calves. We devised a method to allow the cow udder to act as a factory to produce HDPs so that suckling calves will receive a continuous oral dose of HDPs over several weeks to protect them against neonatal diarrhea. We will use Adenovirus to deliver a gene coding for several HDPs in-frame into mammary epithelial cells. The epithelial cells will secrete the HDP protein into milk to be consumed by the suckling calves and trypsin in the calf gut will release the HDPs through cleavage. Thus, the novelty of this research lies not only in the proposed alternative to antibiotics to protect neonates against disease, but in the method by which we introduce the peptides to the suckling offspring.

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乳源性抗菌肽预防新生儿腹泻病:抗生素的替代品
新生儿腹泻病对加拿大和世界各地的畜牧业造成重大经济损失。致病微生物多种多样,包括大肠杆菌、沙门氏菌、轮状病毒、冠状病毒和隐孢子虫。近几十年来,使用抗生素治疗细菌感染和作为饲料中的预防性添加剂大大提高了牛的产量,但减少或消除动物使用抗生素的压力越来越大,这促使畜牧业寻求适当的替代品。抗微生物/宿主防御肽是存在于植物和动物皮肤和分泌物中的天然化合物,对细菌、病毒和寄生虫具有杀微生物作用,并刺激免疫系统对抗传染病。我们的目标是建立口服获得的宿主防御肽(hdp)作为抗生素的替代品,以保护小牛免受新生儿腹泻病。我们设计了一种方法,让奶牛的乳房充当生产HDPs的工厂,这样哺乳的小牛将在几周内连续口服HDPs剂量,以保护它们免受新生儿腹泻的侵害。我们将使用腺病毒将编码帧内HDPs的基因传递到乳腺上皮细胞中。上皮细胞将HDP蛋白分泌到乳汁中供哺乳小牛食用,而小牛肠道中的胰蛋白酶则通过卵裂释放HDP蛋白。因此,这项研究的新颖之处不仅在于提出了抗生素的替代方案,以保护新生儿免受疾病的侵害,而且在于我们将肽引入哺乳后代的方法。
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