Metabolic genes on conjugative plasmids are highly prevalent in Escherichia coli and can protect against antibiotic treatment.

Metabolic genes on conjugative plasmids are highly prevalent in Escherichia coli and can protect against antibiotic treatment.
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DOI:
10.1038/s41396-022-01329-1
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发表时间:
2023-01
期刊:
影响因子:
11
通讯作者:
Lopatkin, Allison J.
Lopatkin, Allison J.
中科院分区:
环境科学与生态学1区
文献类型:
--
作者:
Palomino, Alana;Gewurz, Danya;DeVine, Lela;Zajmi, Ujana;Moralez, Jenifer;Abu-Rumman, Fatima;Smith, Robert P.;Lopatkin, Allison J.

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共轭质粒通常编码抗生素抗性基因,在抗生素治疗期间为其细菌宿主提供选择优势。以前的研究主要认为这些已建立的基因是抗生素介导的质粒传播的主要益处。然而,许多参与细胞代谢过程的基因也可能对抗生素治疗起到保护作用,并提供选择性优势。尽管这些代谢基因的多样性及其潜在的生态影响,但它们的质粒传播患病率、与典型抗生素耐药基因的共存以及表型效应仍未得到广泛的研究。为了解决这一差距,我们将重点放在大肠杆菌上,它通常可以作为病原体,并且已知通过结合传播抗生素抗性基因。我们鉴定了1775个可转移质粒上代谢基因的存在,并将它们的分布与已知的抗生素抗性基因进行了比较。我们发现了大量参与细胞代谢和应激反应的基因。其中一些基因在菌株水平上与已知的抗生素耐药基因表现出统计学上显著的关联或分离,这表明每种基因类型都可能影响其他基因在宿主中的传播。事实上,13个统计相关代谢基因的体外表征证实,它们对抗生素敏感性的表型影响与原位关系基本一致。这些结果强调了代谢基因在共轭质粒上的生态重要性,大肠杆菌病原体的选择动力学是典型机制及其与代谢途径相互作用的复杂结果。
Conjugative plasmids often encode antibiotic resistance genes that provide selective advantages to their bacterial hosts during antibiotic treatment. Previous studies have predominantly considered these established genes as the primary benefit of antibiotic-mediated plasmid dissemination. However, many genes involved in cellular metabolic processes may also protect against antibiotic treatment and provide selective advantages. Despite the diversity of such metabolic genes and their potential ecological impact, their plasmid-borne prevalence, co-occurrence with canonical antibiotic resistance genes, and phenotypic effects remain widely understudied. To address this gap, we focused on Escherichia coli, which can often act as a pathogen, and is known to spread antibiotic resistance genes via conjugation. We characterized the presence of metabolic genes on 1,775 transferrable plasmids and compared their distribution to that of known antibiotic resistance genes. We found high abundance of genes involved in cellular metabolism and stress response. Several of these genes demonstrated statistically significant associations or disassociations with known antibiotic resistance genes at the strain level, indicating that each gene type may impact the spread of the other across hosts. Indeed, in vitro characterization of 13 statistically relevant metabolic genes confirmed that their phenotypic impact on antibiotic susceptibility was largely consistent with in situ relationships. These results emphasize the ecological importance of metabolic genes on conjugal plasmids, and that selection dynamics of E. coli pathogens arises as a complex consequence of both canonical mechanisms and their interactions with metabolic pathways.
细菌群落抗菌素耐药性的生态学和进化。
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