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转座元件如何激活转录沉默的抗生素抗性基因的表达?

How Do Transposable Elements Activate Expression of Transcriptionally Silent Antibiotic Resistance Genes?

机构信息

Department of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096 Warsaw, Poland.

出版信息

Int J Mol Sci. 2022 Jul 22;23(15):8063. doi: 10.3390/ijms23158063.

DOI:10.3390/ijms23158063
PMID:35897639
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9330008/
Abstract

The rapidly emerging phenomenon of antibiotic resistance threatens to substantially reduce the efficacy of available antibacterial therapies. Dissemination of resistance, even between phylogenetically distant bacterial species, is mediated mainly by mobile genetic elements, considered to be natural vectors of horizontal gene transfer. Transposable elements (TEs) play a major role in this process-due to their highly recombinogenic nature they can mobilize adjacent genes and can introduce them into the pool of mobile DNA. Studies investigating this phenomenon usually focus on the genetic load of transposons and the molecular basis of their mobility. However, genes introduced into evolutionarily distant hosts are not necessarily expressed. As a result, bacterial genomes contain a reservoir of transcriptionally silent genetic information that can be activated by various transposon-related recombination events. The TEs themselves along with processes associated with their transposition can introduce promoters into random genomic locations. Thus, similarly to integrons, they have the potential to convert dormant genes into fully functional antibiotic resistance determinants. In this review, we describe the genetic basis of such events and by extension the mechanisms promoting the emergence of new drug-resistant bacterial strains.

摘要

抗生素耐药性这一迅速出现的现象,有可能大幅降低现有抗菌疗法的功效。耐药性的传播,即使在亲缘关系较远的细菌物种之间,主要也是通过可移动的遗传元素来介导的,这些元素被认为是水平基因转移的天然载体。转座元件(Transposable elements,TEs)在这个过程中起着主要作用——由于其高度重组的性质,它们可以动员邻近的基因,并将其引入可移动的 DNA 池中。研究这一现象的研究通常集中在转座子的遗传负荷和它们的移动性的分子基础上。然而,引入进化上不同的宿主的基因不一定会表达。因此,细菌基因组中包含了转录沉默的遗传信息库,这些信息库可以通过各种与转座子相关的重组事件被激活。转座子本身以及与其转座相关的过程,可以将启动子引入随机的基因组位置。因此,与整合子类似,它们有可能将休眠基因转化为完全功能的抗生素耐药决定因素。在这篇综述中,我们描述了这些事件的遗传基础,并由此扩展了促进新的耐药细菌菌株出现的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d50/9330008/689326a157e2/ijms-23-08063-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d50/9330008/fa0af7f1ac8a/ijms-23-08063-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d50/9330008/24dc70bd45b4/ijms-23-08063-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d50/9330008/048a16648634/ijms-23-08063-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d50/9330008/96ebf79730c6/ijms-23-08063-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d50/9330008/689326a157e2/ijms-23-08063-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d50/9330008/fa0af7f1ac8a/ijms-23-08063-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d50/9330008/24dc70bd45b4/ijms-23-08063-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d50/9330008/048a16648634/ijms-23-08063-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d50/9330008/96ebf79730c6/ijms-23-08063-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d50/9330008/689326a157e2/ijms-23-08063-g005.jpg

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