四环素类抗生素耐药研究进展：质粒介导的替加环素耐药机制
Mechanisms of Tetracycline Resistance: Plasmid-Mediated Tigecycline Resistance
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摘要: 抗生素耐药性已成为全球公共卫生的重大挑战。替加环素作为甘氨酰环素类第三代四环素类抗生素，克服了传统四环素类药物的耐药机制，是治疗产碳青霉烯酶多重耐药细菌感染的“最后一道防线”，被世界卫生组织（WHO）列为极其重要的抗生素。然而，随着质粒介导的高水平替加环素耐药基因的出现，替加环素耐药性呈显著上升趋势。替加环素高水平耐药不仅可导致一代、二代四环素药物失效，也可能对新四环素类抗生素形成交叉耐药，其耐药性的传播扩散将对生态安全和公众健康构成严重威胁。本文详述了四环素类抗生素耐药机制的形成与发展，重点阐述了质粒介导的替加环素耐药基因的产生及其在“动物-环境-人类”中的传播过程，最后基于大数据解析了完整细菌基因组中替加环素耐药基因的多种菌株染色体和质粒分布特征，结果可为遏制替加环素耐药性传播扩散提供科学依据。
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关键词:
- 四环素 /
- 替加环素 /
- 耐药机制 /
- 质粒 /
- tet(X)基因家族
Abstract: Antibiotic resistance is a major challenge to global public health. As a new type of tetracycline antibiotic, tigecycline overcomes the main tetracycline resistance mechanisms. Therefore, tigecycline is used for the treatment of infections caused by multidrug-resistant Gram-positive and Gram-negative bacteria, and is considered as a last-resort antibiotic against carbapenem-resistant Enterobacteriaceae infections. However, tigecycline resistance showed an increasing trend after the emergence of plasmid-mediated high-level tigecycline resistance genes. Moreover, high-level tigecycline resistance not only leads to the failure of the first and second generation tetracyclines, but also form cross-resistance to other new tetracyclines. The spread of tigecycline resistance genes in animal-environment-human will pose a serious threat to the ecological safety and public health. At present, the mechanisms of tigecycline resistance include active efflux pump transport system, modified enzyme degradation, mutation of ribosomal protein binding site, mutation of cell membrane, etc. Among them, efflux pump and modified enzyme degradation are the main resistance mechanisms. This paper reviews the development of tetracycline resistance mechanisms, emphatically focuses on the plasmid-mediated tigecycline resistance mechanisms. At last, to obtain the prevalence of tetracycline resistance genes in bacterial genomes and plasmids, we analyze a large number of public available bacterial genomic data. This review paper provides scientific references for further monitoring the spread of tigecycline resistance genes.-
Key words:
- tetracycline /
- tigecycline /
- resistance mechanism /
- plasmid /
- tet(X) gene family
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