Mi Xiaoyu, Wu Lingyun, Song Yanliang, Wang Xiaoyan, Zhu Zhenliang, Zhao Jianglin, Su Jie, Xue Jiaoxiong, Lin Benteng, Gao Dandan, Wang Fei, Feng Rui, Gao Yuanpeng, Liu Jun, Zhang Yong
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, Gansu, China.; College of Veterinary Medicine, Northwest Agriculture & Forestry University, Yangling, Shanxi, 712100, China.
College of Veterinary Medicine, Northwest Agriculture & Forestry University, Yangling, Shanxi, 712100, China.
Int J Biol Macromol. 2025 Feb;290:138922. doi: 10.1016/j.ijbiomac.2024.138922. Epub 2024 Dec 19.
Ruminants possess a rich repository of natural antimicrobial peptides(AMPs) within their bodies, surpassing those found in humans and mice. These peptides, including Defensin, Cathelicidin, and Lysozyme, are integral to the body's innate and adaptive immune responses and represent promising alternatives to antibiotics with significant application potential.
In the present study, we conducted a systematic analysis of 40 Defensins, 38 Cathelicidins, and 61 Lysozymes in cattle and sheep. Our findings revealed that these peptides have retained functional integrity through the evolutionary history of these species. However, they exhibit unique gene duplication and expansion events when compared to humans and mice, indicating their potent roles in cattle and sheep. Notably, the Cathelicidin gene family experienced the most substantial expansion in these ruminants. The newly expanded genes were highly expressed in tissues and organs such as the tongue surface, intestine, mammary gland, and others, exhibiting tissue-specific preferences. This expression pattern is associated with the unique behaviors and high lactation capacity of ruminants. An in vitro bacterial inhibition assay demonstrated that EBD, LALBA, LYSB, and CATHL4 exhibited significant broad-spectrum antibacterial activity. Additionally, loci dB1, dB5, cB2, cB3, and yB1 were pinpointed as key co-regulatory elements in the antimicrobial peptide motifs within cattle mammary epithelial cells.
This research illuminates the structure-function relationship and antimicrobial potency of natural AMP genes in cattle and sheep, providing a theoretical foundation for the development of novel veterinary drugs to treat common bacterial diseases in ruminants and for enhancing animal health care. The identified transcriptional regulatory sites offer a new perspective on the molecular regulation of AMP genes expression, which can be leveraged to improve the disease resistance of domestic animals. This work contributes to a broader understanding of the evolution and regulation of AMP genes, with potential applications for animal health and breeding programs.
反刍动物体内拥有丰富的天然抗菌肽（AMPs）库，比人类和小鼠体内的更为丰富。这些肽包括防御素、组织抗菌肽和溶菌酶，是机体固有免疫和适应性免疫反应的重要组成部分，是具有显著应用潜力的抗生素的有前景的替代品。
在本研究中，我们对牛和羊体内的40种防御素、38种组织抗菌肽和61种溶菌酶进行了系统分析。我们的研究结果表明，这些肽在这些物种的进化历史中保留了功能完整性。然而，与人类和小鼠相比，它们表现出独特的基因复制和扩增事件，表明它们在牛和羊中发挥着重要作用。值得注意的是，组织抗菌肽基因家族在这些反刍动物中经历了最显著的扩增。新扩增的基因在舌表面、肠道、乳腺等组织和器官中高度表达，表现出组织特异性偏好。这种表达模式与反刍动物独特的行为和高泌乳能力有关。体外细菌抑制试验表明，EBD、LALBA、LYSB和CATHL4表现出显著的广谱抗菌活性。此外，位点dB1、dB5、cB2、cB3和yB1被确定为牛乳腺上皮细胞抗菌肽基序中的关键共调控元件。
本研究阐明了牛和羊体内天然AMPs基因的结构-功能关系和抗菌效力，为开发治疗反刍动物常见细菌疾病的新型兽药和加强动物保健提供了理论基础。鉴定出的转录调控位点为AMPs基因表达的分子调控提供了新的视角，可用于提高家畜的抗病能力。这项工作有助于更广泛地理解AMPs基因的进化和调控，对动物健康和育种计划具有潜在应用价值。
