猪源抗菌肽分子改造与应用进展

Molecular Modification and Application of Porcine Antimicrobial Peptides

抗菌肽(AMPs)是动植物、微生物中普遍存在的一种小肽类物质,多数具有广谱抗菌活性,已逐渐发展为替代抗生素的有力候选者之一。猪源AMPs是第一批从哺乳动物中分离得到的AMPs,已发现有30多种,主要包括Cathelicidins家族和防御素(defensins)家族。这些猪源AMPs抗菌机制与抗生素不尽相同,其可以与细菌细胞膜相互作用破坏膜的完整性,最终导致细菌细胞内容物泄漏并杀死细菌,因此不易产生耐药性。但天然猪源AMPs还存在稳定性差、细胞毒性高及规模生产成本高等问题,目前的研究在于先后开发了氨基酸替换、序列截断、杂合、结构优化和/或脂肪酸修饰等方法,以期获得兼具高效和低毒的短序列AMPs。本文根据猪源AMPs的来源家族进行分类,并对其二级结构、抑菌机制及现阶段的改造和应用状况进行了综述。

Antimicrobial peptides(AMPs)are small peptides that are commonly found in plants,animals and microorganisms.Most of them exhibit broad-spectrum antibacterial prowess and are considered to be a promising candidate for antibiotics.The porcine AMPs are the first batch isolated from mammals.To data,over 30 porcine AMPs with elucidated sequences have been identified,with the predominant families being Cathelicidins and defensins.The bactericidal mechanism of these porcine AMPs diverges significantly from conventional antibiotics by interacting directly with the bacterial cell membrane,compromising its impermeability,inducing cellular leakage and culminating in cell death.The non-specific membrane rupture mechanism is not prone to produce drug resistance.However,natural porcine AMPs still have limitations such as poor stability,high cytotoxicity and prohibitive cost for large-scale production.Researchers have developed methods such as residue substitution,sequence truncation,motif hybridization,structure optimization and/or fatty acid modification to obtain short-sequence AMPs with both efficiency and biocompatibility.This review attempts to categorize porcine AMPs based on their original classification,while providing a comprehensive overview of their secondary structure,action mechanism,molecular modifications,and prospective applications.