N-乙酰半胱氨酸作为细菌抗生物膜佐剂：机制、协同组合与临床转化。

文献信息

中文摘要

N-乙酰半胱氨酸（NAC）是L-半胱氨酸的一种合成衍生物，自20世纪中叶以来已知其具有黏液溶解作用，近几十年来因其抗氧化和抗生物膜特性而受到关注。细菌生物膜是包裹在细胞外聚合物基质中的结构化微生物群落，这导致其对抗生素的耐药性显著增加（比浮游形式高达1000倍）以及对宿主免疫应答的抵抗。根据文献，高达65%的感染因子与生物膜形成相关，使其成为具有挑战性的治疗靶点。本综述系统整理了关于NAC抗生物膜作用的分子机制的当前数据，包括破坏基质蛋白和多糖、降解细胞外DNA、抑制群体感应系统以及干扰细菌氧化还原稳态。特别关注NAC与五大类抗生素的协同组合；提供了有效浓度，并描述了相互作用类型。综述了最近十年的临床研究结果，证明NAC作为尿路感染、慢性鼻窦炎、糖尿病性骨髓炎和囊性纤维化辅助治疗的潜力。批判性评估了主要局限性（pH依赖性、不稳定性、口服生物利用度低），并提出了利用纳米颗粒、水凝胶以及与蜂胶或壳聚糖组合来克服这些局限性的方法。本综述面向抗菌化疗研究人员和新型药物递送系统开发者。

英文摘要

N-acetylcysteine (NAC) is a synthetic derivative of L-cysteine, known since the mid-20th century as a mucolytic agent and, in recent decades, has attracted attention for its antioxidant and antibiofilm properties. Bacterial biofilms are structured communities of microorganisms enclosed in an extracellular polymeric matrix, which accounts for their markedly increased resistance to antibiotics (up to 1000-fold higher than in planktonic forms) and to the host immune response. According to the literature, up to 65% of infectious agents are associated with biofilm formation, making them a challenging therapeutic target. This review systematizes current data on the molecular mechanisms of the antibiofilm action of NAC, including disruption of matrix proteins and polysaccharides, degradation of extracellular DNA, suppression of the quorum sensing system, and disturbance of bacterial redox homeostasis. Particular attention is given to synergistic combinations of NAC with antibiotics of five major classes; effective concentrations are provided, and the types of interaction are characterized. The results of clinical studies from the last decade are reviewed, demonstrating the potential of NAC as an adjuvant in urinary tract infections, chronic rhinosinusitis, diabetic osteomyelitis, and cystic fibrosis. The main limitations (pH dependence, instability, low oral bioavailability) are critically evaluated, and approaches to overcoming them using nanoparticles, hydrogels, and combinations with propolis or chitosan are proposed. The review is intended for researchers in antimicrobial chemotherapy and developers of new drug delivery systems.