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摘要: 细菌耐药性的持续蔓延已成为全球公共卫生领域的重大挑战。噬菌体衍生的内溶素因其独特的抗菌机制,逐渐成为传统抗生素的潜在替代策略。内溶素是噬菌体编码的肽聚糖水解酶,通过裂解细菌细胞壁发挥杀菌作用,具有宿主特异性强、不易耐药、菌群干扰小及多靶点协同等优势。内溶素在人类医学、兽医学及食品工业等领域中对多种耐药菌表现出强效裂解活性。内溶素与传统抗生素联合应用可产生协同效应,显著降低抗生素的最低抑菌浓度,并提高感染模型的生存率。对内溶素作为新型抗菌剂的应用及作用机制进展进行综述,以期为后续将噬菌体内溶素应用于细菌耐药性感染的研究提供参考。Abstract: [Abstract] The continued spread of bacterial antibiotic resistance has become a major challenge in global public health. Endolysins derived from bacteriophages, with their unique antimicrobial mechanisms, are gradually emerging as a potential alternative to traditional antibiotics. Endolysins are peptidoglycan hydrolases encoded by bacteriophages that exert bactericidal effects by lysing bacterial cell walls, with advantages such as strong host specificity, low propensity for resistance development, minimal disruption to the microbiota, and synergistic multi-target mechanisms . Endolysins have demonstrated potent lytic activity against various antibiotic-resistant bacteria in human medicine, veterinary medicine, and the food industry. When combined with conventional antibiotics, endolysins can produce synergistic effects, significantly reducing the minimum inhibitory concentration of antibiotics and improving survival rates in infection models. This review summarizes the application and mechanisms of action of endolysins as novel antimicrobial agents, with the aim of providing reference for future research on the application of bacteriophage endolysins in treating bacterial antibiotic-resistant infections.
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Key words:
- Endolysin /
- Bacteriophage /
- Phage therapy /
- Bacterial resistance
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表 1 抗生素、噬菌体和内溶素抗菌特性对比
Table 1. Comparison of antibacterial properties of antibiotics,bacteriophages,and endolysins
特性维度 抗生素 噬菌体 内溶素 参考文献 杀菌特异性 广谱/窄谱,易扰乱微生态 种/株特异性极强,精准靶向致病菌 相对广谱的溶菌活性,可作用于多种口腔革兰氏阳性/阴性菌 [14−15] 增殖特性 非增殖,浓度依赖 在宿主菌内自我增殖,理论上单次给药可放大效应 非增殖,作用剂量可精确控制 [16−17] 作用方式 干扰细菌关键代谢(如细胞壁合成、蛋白合成) 劫持宿主菌代谢系统,破坏多个核心生物学过程 胞外酶解作用,靶向水解肽聚糖中特定化学键 [15,18] 杀菌速度 起效较慢,需数小时至数天 依赖感染周期,裂解释放耗时长 快速裂解,接触后数秒至数分钟内即发挥杀菌效应 [19−20] 胞内活性 部分可穿透宿主细胞膜,治疗胞内菌感染 无法穿透真核细胞膜,对胞内菌无效 天然活性有限,但经融合细胞穿透肽等改造后可增强胞内递送 [20−21,65] 耐药性风险 广泛存在且日益严重 细菌可通过受体突变等机制产生抗噬菌体性 至今未见临床耐药报道,可有效应对多重耐药菌株 [22−23] 抗生物被膜能力 渗透受限,对成熟生物膜效果差 渗透能力有限,难以清除生物膜深层细菌 可穿透生物膜基质,直接裂解其中细菌,破坏生物膜结构 [15,37] 免疫原性 多数无免疫原性 可被机体免疫系统识别并产生中和抗体 免疫原性较低,抗体中和作用较弱 [24,59,64] 药代动力学 体内过程明确,浓度-效应关系清晰 体内行为复杂,临床证据有限 可定量测定感染部位及血药浓度 [22−23,60] -
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