新型可移动RND家族外排泵TMexCD-TOprJ的研究进展

Research progress in a novel mobile RND efflux pump TMexCD-TOprJ

摘要:

抗生素被认为是现代医学的基石之一，但包括抗生素在内抗菌药物的滥用也加速了可抵抗多种抗菌药物“超级细菌”的出现。耐药基因是导致细菌产生耐药性的关键因素，可通过质粒、转座子(transposon, Tn)、插入序列(insertion sequence, IS)等可移动元件(mobile genetic elements, MGEs)进行水平转移，严重威胁公共卫生安全。近年来，面对碳青霉烯类药物和多黏菌素耐药性的暴发，替加环素被视为人类面临多重耐药细菌感染的最后一道防线。近期发现了一种主要存在于质粒上的新型可移动外排泵基因簇tmexCD-toprJ，可编码耐药结节细胞分化家族(resistance-nodulation-cell division, RND)外排泵，排出菌体内包括替加环素在内的多种抗生素，大幅提升了细菌的耐药性。tmexCD-toprJ基因簇可以随质粒等可移动元件进行水平转移，已经传播至人、动物和环境中，给公共卫生健康造成了严重威胁。然而，目前人们对于其具体结构和功能作用机制等研究仍不透彻。本文系统总结tmexCD-toprJ耐药基因的分布特征、传播机制及外排泵结构等研究现状，并基于同一健康(One Health)理念提出了阻遏其扩散的措施，为减缓tmexCD-toprJ传播提供科学依据。

Abstract:

Antibiotics are considered one of the cornerstones of modern medicine. However, the abuse of antimicrobial agents, including antibiotics, has accelerated the emergence of super bacteria that can resist multiple antimicrobial agents. Resistance genes are the key factors leading to bacterial resistance and can be horizontally transmitted by mobile genetic elements (MGEs), such as plasmids, transposons, and insertion sequences, posing a serious threat to public health. In recent years, facing the outbreak of carbapenem-resistant and polymyxin-resistant bacteria, tigecycline has been regarded as the “last line of defense” against multiple drug-resistant bacterial infections in humans. Recently, a novel mobile efflux pump gene cluster tmexCD-toprJ, mainly existing in plasmids, was found. This gene cluster encodes resistance-nodulation-cell division (RND) efflux pumps, which can expel a variety of antibiotics, including tigecycline, out of bacteria, greatly enhancing the resistance of bacteria. The tmexCD-toprJ gene cluster has been horizontally transferred to humans, animals, and the environment by mobile elements such as plasmids, posing a serious threat to public health. However, research on the specific structure and functional mechanism of TMexCD-TOprJ remains to be carried out. This article systematically summarizes the distribution characteristics, transmission mechanisms, and efflux pump structures of tmexCD-toprJ and proposes measures to block its spread from the concept of One Health, offering a scientific basis for slowing down the dissemination of tmexCD-toprJ.