Multidrug resistance plasmids commonly reprogram the expression of metabolic genes in Escherichia coli
Multidrug resistance plasmids commonly reprogram the expression of metabolic genes in Escherichia coli
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DOI：
10.1128/msystems.01193-23
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发表时间：
2024-02-20
期刊：
影响因子：
6.4
通讯作者：
McNally，Alan
中科院分区：
文献类型：
--
作者：
Hall，Rebecca J.;Snaith，Ann E.;McNally，Alan
无标签：耐多药的大肠杆菌是全球死亡的主要原因。携带编码β-内酰胺酶、碳青霉素酶和粘菌素耐药性基因的质粒在谱系之间的转移正在推动难以治疗的医院和社区感染的上升。多药耐药(MDR)质粒的获得通常会导致转录中断，虽然一些研究表明MDR质粒在不同细菌谱系中的菌株特异性适合性和转录效应，但很少有研究比较不同MDR质粒在常见细菌宿主中的影响。因此，我们预测哪些MDR质粒最有可能在细菌群体中保持和传播的能力是有限的。在这里，我们将编码对一系列临床重要抗生素的耐药性的八种不同的MDR质粒引入到E.ColiK-12 MG1655中，并测量了它们的适合性成本和转录影响。转录反应的规模在不同的质粒之间有很大的不同，从差异表达的>；650到<；20个染色体基因。然而，调控中断的规模与质粒适应成本的大小没有明显的相关性，这也在不同的质粒之间有所不同。不同接合子差异表达基因的同源性不同，尽管某些代谢基因的表达和功能受到多个质粒的共同影响，包括参与L蛋氨酸转运和代谢的基因下调。我们的数据显示了宿主遗传背景和质粒遗传背景之间相互作用的复杂性，以确定获得多药耐药质粒对大肠杆菌的影响。重要：对多种抗生素耐药的感染增加，包括那些携带碳青霉素酶、β-内酰胺酶和粘菌素耐药基因的菌株，引起全球关注。这些抗性中的许多是通过接合的质粒传播的。更多地了解分离物如何对编码抗生素耐药性的传入质粒做出反应，将提供可用于预测MDR谱系出现的信息。在这里，新陈代谢网络对进入的质粒特别敏感的识别提示了减少质粒转移的可能目标。
UNLABELLED: Multidrug-resistant Escherichia coli is a leading cause of global mortality. Transfer of plasmids carrying genes encoding beta-lactamases, carbapenamases, and colistin resistance between lineages is driving the rising rates of hard-to-treat nosocomial and community infections. Multidrug resistance (MDR) plasmid acquisition commonly causes transcriptional disruption, and while a number of studies have shown strain-specific fitness and transcriptional effects of an MDR plasmid across diverse bacterial lineages, fewer studies have compared the impacts of different MDR plasmids in a common bacterial host. As such, our ability to predict which MDR plasmids are the most likely to be maintained and spread in bacterial populations is limited. Here, we introduced eight diverse MDR plasmids encoding resistances against a range of clinically important antibiotics into E. coli K-12 MG1655 and measured their fitness costs and transcriptional impacts. The scale of the transcriptional responses varied substantially between plasmids, ranging from> 650 to< 20 chromosomal genes being differentially expressed. However, the scale of regulatory disruption did not correlate significantly with the magnitude of the plasmid fitness cost, which also varied between plasmids. The identities of differentially expressed genes differed between transconjugants, although the expression of certain metabolic genes and functions were convergently affected by multiple plasmids, including the downregulation of genes involved in L-methionine transport and metabolism. Our data show the complexity of the interaction between host genetic background and plasmid genetic background in determining the impact of MDR plasmid acquisition on E. coli.IMPORTANCE: The increase in infections that are resistant to multiple classes of antibiotics, including those isolates that carry carbapenamases, beta-lactamases, and colistin resistance genes, is of global concern. Many of these resistances are spread by conjugative plasmids. Understanding more about how an isolate responds to an incoming plasmid that encodes antibiotic resistance will provide information that could be used to predict the emergence of MDR lineages. Here, the identification of metabolic networks as being particularly sensitive to incoming plasmids suggests the possible targets for reducing plasmid transfer.