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抗生素耐药性基因根据耐药性机制进行不同程度的动员

发布者:抗性基因网 时间:2023-05-26 浏览量:219

摘要
出身背景
用(元)基因组测序在特别是环境样本中筛选抗生素耐药性基因(ARGs)与表型耐药性的假阳性预测有关。这源于这样一个事实,即大多数获得性ARGs在赋予抗性之前需要过表达,这通常是由移动遗传元件(MGE)对假定的ARGs的去结构化引起的。ARGs的过度表达可能是由插入序列(IS)元件和整合素中经常存在的强启动子以及质粒的拷贝数效应引起的,这可能有助于辅助基因的高表达。
后果
在这里,我们对所有完整的细菌RefSeq基因组进行ARGs筛选。研究了检测到的ARGs的遗传背景,包括IS元件、整合子、质粒和系统发育分散。提出了ARG-MOB量表,该量表表明检测到的ARG在细菌基因组中是如何动员的。结论是,在15790个研究的基因组中,抗生素外排基因很少被动员,甚至80%的β-内酰胺酶从未或很少被动员。然而,一些ARG确实被动员起来,并与IS元件、质粒和整合素共同存在。
结论
在这项研究中,使用所提出的ARG-MOB量表,根据所有完整细菌基因组中的ARGs与MGE的关联进行分类。这些结果对筛选耐药性决定因素的研究的设计和解释产生了影响,因为动员的ARG对人类健康构成了更具体的风险。为未来针对高度动员的ARG的研究提供了所有结果的交互式表格。
Abstract
Background
Screening for antibiotic resistance genes (ARGs) in especially environmental samples with (meta)genomic sequencing is associated with false-positive predictions of phenotypic resistance. This stems from the fact that most acquired ARGs require being overexpressed before conferring resistance, which is often caused by decontextualization of putative ARGs by mobile genetic elements (MGEs). Consequent overexpression of ARGs can be caused by strong promoters often present in insertion sequence (IS) elements and integrons and the copy number effect of plasmids, which may contribute to high expression of accessory genes.

Results
Here, we screen all complete bacterial RefSeq genomes for ARGs. The genetic contexts of detected ARGs are investigated for IS elements, integrons, plasmids, and phylogenetic dispersion. The ARG-MOB scale is proposed, which indicates how mobilized detected ARGs are in bacterial genomes. It is concluded that antibiotic efflux genes are rarely mobilized and even 80% of β-lactamases have never, or very rarely, been mobilized in the 15,790 studied genomes. However, some ARGs are indeed mobilized and co-occur with IS elements, plasmids, and integrons.

Conclusions
In this study, ARGs in all complete bacterial genomes are classified by their association with MGEs, using the proposed ARG-MOB scale. These results have consequences for the design and interpretation of studies screening for resistance determinants, as mobilized ARGs pose a more concrete risk to human health. An interactive table of all results is provided for future studies targeting highly mobilized ARGs.

https://academic.oup.com/gigascience/article/doi/10.1093/gigascience/giac072/6652189?login=false