持留菌形成机制和清除策略研究进展

doi:10.3969/j.issn.1673-8640.2023.08.016

摘要/Abstract

摘要：

持留菌虽然很早即被发现，但是在抗感染诊疗中较少被提及。随着抗菌药物耐药和抗药性问题的日益严重，相关研究不断深入。病原菌持留现象已被发现于大多数细菌，并被认为是导致慢性感染和疾病迁延不愈的重要原因。持留菌的形成机制涉及多种细胞生命过程，但具体机制目前尚不明确。近年来，临床针对持留菌的治疗策略已基本形成共识。文章对持留菌形成机制相关研究、临床应对策略进行综述，以期为解决慢性感染性疾病治疗中所面临的重大挑战有所帮助。

关键词: 持留菌, 机制, 清除, 抗感染, 耐药

Abstract:

Although bacterial persister has been found for a long time，they are rarely mentioned in anti-infective diagnosis and treatment. With the increasingly serious problem of antibiotic resistance and tolerance and the deepening of research，bacterial persistence has been found in most bacteria，and it is considered to be a cause of chronic infection and disease delay. The mechanism of bacterial persister formation involves many cell life processes，but it is still not completely clear. There is a consensus on the treatment strategy for bacterial persisters. This review focuses on the mechanism research of bacterial persisters and the treatment strategies in the recent years，so as to solve the major challenge in the treatment of chronic infectious diseases.

Key words: Bacterial persister, Mechanism, Eradication, Anti-infection, Drug resistance

中图分类号:

R446.1

王朝, 赵煜. 持留菌形成机制和清除策略研究进展[J]. 检验医学, 2023, 38(8): 790-795.

WANG Chao, ZHAO Yu. Research progress on formation mechanism and eradication strategy of bacterial persisters[J]. Laboratory Medicine, 2023, 38(8): 790-795.

图/表 1

参考文献 42

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名称	类型	作用机制	作用菌种	参考文献
CD437和CD1530	合成类视黄醇	破坏脂质双层	耐甲氧西林金黄色葡萄球菌持留菌	[21]
α/β嵌合多肽分子刷	宿主防御肽聚合物模拟物	干扰细胞膜，增加ROS水平	耐甲氧西林金黄色葡萄球菌生物膜和持留菌	[22]
万古霉素-D-八精氨酸	双功能抗菌药物-转运蛋白偶联物	在分子转运蛋白的协助下，万古霉素阻止细胞壁组装，抑制胱硫氨酸γ裂解酶	耐甲氧西林金黄色葡萄球菌生物膜和持留菌	[23]
NL1、NL2、NL3	小分子酶抑制剂	在分子转运蛋白的协助下，万古霉素阻止细胞壁组装，抑制胱硫氨酸γ裂解酶	金黄色葡萄球菌持留菌和铜绿假单胞菌持留菌	[24]
SPI009	小分子化合物	广泛破坏生物膜，增强协同抗菌药物活性	铜绿假单胞菌持留菌	[25]
N-芳基化NH125类似物1	膜活性双亲性化合物，季铵阳离子	引起细胞膜去极化，破坏脂质双层	耐甲氧西林金黄色葡萄球菌持留菌	[26-27]
聚（乙酰，精氨酰）氨基葡萄糖	大分子阳离子含糖聚合物	增加细胞膜通透性，引起细胞膜去极化	铜绿假单胞菌持留菌	[28]

名称	类型	作用机制	作用菌种	参考文献
CD437和CD1530	合成类视黄醇	破坏脂质双层	耐甲氧西林金黄色葡萄球菌持留菌	[21]
α/β嵌合多肽分子刷	宿主防御肽聚合物模拟物	干扰细胞膜，增加ROS水平	耐甲氧西林金黄色葡萄球菌生物膜和持留菌	[22]
万古霉素-D-八精氨酸	双功能抗菌药物-转运蛋白偶联物	在分子转运蛋白的协助下，万古霉素阻止细胞壁组装，抑制胱硫氨酸γ裂解酶	耐甲氧西林金黄色葡萄球菌生物膜和持留菌	[23]
NL1、NL2、NL3	小分子酶抑制剂	在分子转运蛋白的协助下，万古霉素阻止细胞壁组装，抑制胱硫氨酸γ裂解酶	金黄色葡萄球菌持留菌和铜绿假单胞菌持留菌	[24]
SPI009	小分子化合物	广泛破坏生物膜，增强协同抗菌药物活性	铜绿假单胞菌持留菌	[25]
N-芳基化NH125类似物1	膜活性双亲性化合物，季铵阳离子	引起细胞膜去极化，破坏脂质双层	耐甲氧西林金黄色葡萄球菌持留菌	[26-27]
聚（乙酰，精氨酰）氨基葡萄糖	大分子阳离子含糖聚合物	增加细胞膜通透性，引起细胞膜去极化	铜绿假单胞菌持留菌	[28]