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在转基因小鼠中组成性表达抗菌肽 PR-39 可显著增强其对细菌感染的抵抗力并促进其生长。

Constitutive expression of antimicrobial peptide PR-39 in transgenic mice significantly enhances resistance to bacterial infection and promotes growth.

机构信息

College of Marine Science, South China Agricultural University, Guangzhou, 510642, China.

National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.

出版信息

Transgenic Res. 2018 Oct;27(5):409-422. doi: 10.1007/s11248-018-0084-z. Epub 2018 Jul 12.

Abstract

Use of huge amounts of antibiotics in farm animal production has promoted the prevalence of antibiotic-resistant bacteria, which poses a serious threat to public health. Therefore, alternative approaches are needed to reduce or replace antibiotic usage in the food animal industry. PR-39 is a pig-derived proline-rich antimicrobial peptide that has a broad spectrum of antibacterial activity and a low propensity for development of resistance by microorganisms. To test whether ubiquitous expression of PR-39 in transgenic (TG) mice can increase resistance against bacterial infection, we generated TG mice that ubiquitously express a pig-derived antimicrobial peptide PR-39 and analyzed their growth and resistance to infection of the highly pathogenic Actinobacillus pleuropneumoniae (APP) isolated from swine. The growth performance was significantly increased in TG mice compared with their wild-type (WT) littermates. After the APP challenge, TG mice exhibited a significantly higher survival rate and significantly lower tissue bacterial load than WT littermates. Furthermore, the tissue lesion severity that resulted from APP infection was milder in TG mice than that in their WT littermates. This study provides a good foundation for the development of PR-39-expressing TG animals, which could reduce the use of antibiotics in the farm animal industry.

摘要

在畜牧业生产中大量使用抗生素促进了抗生素耐药菌的流行,这对公共卫生构成了严重威胁。因此,需要替代方法来减少或替代食品动物产业中抗生素的使用。PR-39 是一种来源于猪的富含脯氨酸的抗菌肽,具有广谱的抗菌活性,微生物产生耐药性的倾向较低。为了测试 PR-39 在转基因 (TG) 小鼠中的普遍表达是否可以提高对细菌感染的抵抗力,我们生成了普遍表达猪源性抗菌肽 PR-39 的 TG 小鼠,并分析了它们的生长情况和对来自猪的高致病性胸膜肺炎放线杆菌 (APP) 的感染抵抗能力。与野生型 (WT) 同窝仔鼠相比,TG 小鼠的生长性能显著提高。在 APP 挑战后,TG 小鼠的存活率明显高于 WT 同窝仔鼠,组织细菌负荷明显低于 WT 同窝仔鼠。此外,APP 感染导致的组织病变严重程度在 TG 小鼠中比 WT 同窝仔鼠中较轻。这项研究为开发表达 PR-39 的 TG 动物提供了良好的基础,这可以减少畜牧业生产中抗生素的使用。

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