It is consensus that clinically relevant antibiotic resistance genes have their origin in environmental bacteria, including the large pool of primarily benign species. Yet, for the vast majority of acquired antibiotic resistance genes, the original environmental host(s) have not been identified to date. Closing this knowledge gap could improve our understanding of how antimicrobial resistance proliferates in the bacterial domain and shed light on the crucial step of initial resistance gene mobilization in particular. Here, we combine information from publicly available long- and short-read environmental metagenomes as well as whole-genome sequences to identify the original environmental hosts of dfrB, a family of genes conferring resistance to trimethoprim. Although this gene family stands in the shadow of the more widespread, structurally different dfrA, it has recently gained attention through the discovery of several new members. Based on the genetic context of dfrB observed in long-read metagenomes, we predicted bacteria of the order Burkholderiales to function as original environmental hosts of the predominant gene variants in both soil and freshwater. The predictions were independently confirmed by whole-genome datasets and statistical correlations between dfrB abundance and taxonomic composition of environmental bacterial communities. Our study suggests that Burkholderiales in general and the family Comamonadaceae in particular represent environmental origins of dfrB genes, some of which now contribute to the acquired resistome of facultative pathogens. We propose that our workflow centered around long-read environmental metagenomes allows for the identification of the original hosts of further clinically relevant antibiotic resistance genes.

中文翻译：

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Burkholderiales 目细菌是 II 型甲氧苄啶耐药基因 （dfrB） 的原始环境宿主


临床相关的抗生素耐药基因起源于环境细菌，包括大量主要良性物种，这是共识。然而，对于绝大多数获得性抗生素耐药基因，迄今为止尚未确定原始环境宿主。缩小这一知识差距可以提高我们对抗菌素耐药性如何在细菌领域增殖的理解，特别是阐明初始耐药基因动员的关键步骤。在这里，我们结合了来自公开可用的长读长和短读长环境宏基因组以及全基因组序列的信息，以确定 dfrB 的原始环境宿主，dfrB 是一个赋予甲氧苄啶耐药性的基因家族。尽管这个基因家族处于更广泛、结构不同的 dfrA 的阴影下，但它最近通过发现几个新成员而受到关注。基于在长读长宏基因组中观察到的 dfrB 的遗传背景，我们预测 Burkholderiales 目细菌将作为土壤和淡水中主要基因变异的原始环境宿主发挥作用。全基因组数据集和 dfrB 丰度与环境细菌群落分类组成之间的统计相关性独立证实了这些预测。我们的研究表明，Burkholderiales 一般，特别是 Comamonadaceae 科代表了 dfrB 基因的环境起源，其中一些基因现在有助于兼性病原体的获得性抵抗组。我们建议我们以长读长环境宏基因组为中心的工作流程允许识别进一步临床相关的抗生素耐药基因的原始宿主。