新型四环素灭活酶tet(X)致替加环素耐药的机制研究进展
Advances in mechanism study on novel tetracycline-inactivating enzymes tet(X) causing emerging tigecycline resistance
Received date: 2022-03-07
Online published: 2023-07-06
细菌的抗生素耐药性已成为全球公共健康的巨大威胁。替加环素是新一代的四环素类药物，是目前治疗耐碳青霉烯类革兰氏阴性菌感染的最后一道防线。然而可移动新型四环素灭活酶tet(X)直系同源物的出现，导致了高水平替加环素耐药。目前，已经发现tet(X)的同系物主要有tet(X1)、tet(X2)、tet(X3)、tet(X3.2)、tet(X4)、tet(X5)、tet(X6)和tet(X7)。该耐药基因已经传播到世界多个地区医院中相关的患者和环境中，涉及多种不同种类的细菌，其中携带tet(X3)和tet(X4)基因的耐药细菌表现出最高的耐药水平。耐药机制中，插入序列ISCR2与tet(X3)、tet(X4)、tet(X5)的水平传播密切相关，位于多种型别质粒上tet(X4)的基因遗传结构较为复杂，可位于各式各样的可移动原件上，加速了该耐药基因的播散。质粒介导的替加环素耐药性可能会进一步扩散到各种生态位和临床高危病原体中。迫切需要临床及科研工作者共同努力，来阻止该耐药基因的传播。
沈平华, 陈慧芬 . 新型四环素灭活酶tet(X)致替加环素耐药的机制研究进展[J]. 诊断学理论与实践, 2023 , 22(01) : 75 -79 . DOI: 10.16150/j.1671-2870.2023.01.012
Antibiotic resistance in bacteria has become a great threat to global public health. Tigecycline is a next-generation tetracycline that is the final line of defense against severe infections by carbapenem-resistant Gram-negative bacteria. Unfortunately, this last-resort antibiotic has been challenged by the recent emergence of the mobile tet(X) orthologs that can confer high-level tigecycline resistance. This review will systematically introduce the latest progress in the type, distribution and dissemination, and genetic environment of this orthologs. At present, orthologs of tet(X) mainly include tet(X1), tet(X2), tet(X3), tet(X3.2), tet(X4), tet(X5), tet(X6) and tet(X7). The resistance gene has already been reported in a variety of bacterial hosts and spread to hospital-associated patients and environment in multiple countries/regions. The bacteria carrying tet(X3) and tet(X4) shows the highest resistance level. The insertion sequence ISCR2 is closely related to the horizontal spread of tet(X3), tet(X4) and tet(X5). In particular, the genetic environment of tet(X4) on plasmids is complex, that can be located on various mobile elements, which accelerates the spread of the drug resistance gene. The plasmid-mediated tigecycline resistance may further spread into a variety of ecological niches and into clinical high-risk pathogens and collective efforts are in urgent need to further strengthen the surveillance and research on tigecycline resistance.
Key words： Tigecycline; Resistance mechanisms; Tet(X); Horizontal spread
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