The Association between Insertion Sequences and Antibiotic Resistance Genes
The Association between Insertion Sequences and Antibiotic Resistance Genes
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DOI：
10.1128/msphere.00418-20
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发表时间：
2020-09-01
期刊：
影响因子：
4.8
通讯作者：
Larsson, D. G. Joakim
中科院分区：
文献类型：
--
作者：
Razavi, Mohammad;Kristiansson, Erik;Larsson, D. G. Joakim
插入序列（Insertion sequences，IS）是细菌基因组上丰富的移动的遗传元件，负责包括抗生素抗性基因（antibiotic resistance genes，ARGs）在内的许多基因的移动。由于ARG通常发生在相似的遗传背景下，了解哪些IS倾向于与已知的ARG相关，这可能是通过预测或实验策略发现新ARG的第一步。这可能是有价值的，因为早期识别病原体中的ARG可以促进监测，限制行动，分子诊断和药物开发。在这里，我们提出了一个全面的分析特定的IS与已知的ARG的关联。大量的细菌基因组被用来表征2,437个已知ARG和3,768个IS的直接背景。虽然许多ARG始终被发现接近特定的IS，所有IS周围的环境更加多变。然而，一个子集的个别IS，以及暂定的复合转座子，显示出显着的协会与ARG。这些措施包括，156、Tn 3、IS 4和IS 1等插入序列不仅与不同的ARG密切相关，而且在病原体中高度丰富。因此，我们得出结论，这一子集的IS和暂定复合转座子的背景下，将是特别有价值的发现新的ARGs通过建模或经验的方法。分析了一组1，891个宏基因组，以确定通常与ARG相关的IS特别丰富的环境。在宏基因组中发现的关联与在基因组中发现的关联相似。重要性病原体中抗生素耐药基因（ARG）的出现和传播威胁着细菌感染的预防和治疗以及我们的食品生产链。早期了解病原体中存在的或有可能成为临床相关的移动的ARG可能有助于减轻潜在的负面后果。最近，探索整合子基因盒被证明是成功的，以确定新的动员ARG，其中一些已经在病原体中循环。尽管如此，只有一个子集的ARG是动员整合子，和其他移动的遗传因素与ARG的背景仍然没有探索。这包括负责许多ARG动员的插入序列（IS）。我们的分析确定了IS，物种和环境，其中ARG-IS关系特别强。这可能是指导发现新型ARG的第一步，同时也为ARG的动员和转移机制提供了见解。
Insertion sequences (ISs) are abundant mobile genetic elements on bacterial genomes, responsible for mobilization of many genes, including antibiotic resistance genes (ARGs). As ARGs often occur in similar genetic contexts, understanding which ISs tend to be associated with known ARGs could be a first step toward discovering novel ARGs through predictive or experimental strategies. This could be valuable, as early identification of ARGs in pathogens could facilitate surveillance, confinement actions, molecular diagnostics, and drug development. Here, we present a comprehensive analysis of the association of specific ISs with known ARGs. A large collection of bacterial genomes was used to characterize the immediate context of 2,437 known ARGs and 3,768 ISs. While many ARGs were consistently found close to specific ISs, the contexts around all ISs were more variable. Nevertheless, a subset of individual ISs, as well as tentative composite transposons, showed significant associations with ARGs. These included, e.g., insertion sequences classified as 156, Tn3, IS4, and IS1 that were not only strongly associated with diverse ARGs but also highly abundant in pathogens. Therefore, we conclude that the context of this subset of ISs and tentative composite transposons would be particularly valuable to discover novel ARGs through modeling or empirical approaches. A set of 1,891 metagenomes were analyzed to identify environments where those ISs commonly associated with ARGs were particularly abundant. The associations found in metagenomes were similar to those found in genomes.IMPORTANCE The emergence and spread of antibiotic resistance genes (ARGs) among pathogens threaten the prevention and treatment of bacterial infections as well as our food production chains. Early knowledge about mobile ARGs that are present in pathogens or that have the potential to become clinically relevant could help mitigate potential negative consequences. Recently, exploring integron gene cassettes was shown to be successful for identifying novel mobilized ARGs, some of which were already circulating in pathogens. Still, only a subset of ARGs is mobilized by integrons, and the contexts of other mobile genetic elements associated with ARGs remain unexplored. This includes insertion sequences (ISs) responsible for the mobilization of many ARGs. Our analyses identified ISs, species, and environments where ARG-IS relationships are particularly strong. This could be a first step to guide the discovery of novel ARGs, while also providing insights into mechanisms involved in the mobilization and transfer of ARGs.