摘要

       抗生素抗性基因 (ARG) 被插入序列 (IS) 元件、质粒和整合子动员的程度与其作为抗性决定因素的可能性有很强的关联。这源于遗传去上下文化，其中强启动子通常存在于 IS 元件和整合子中，而质粒的拷贝数效应有助于辅助基因的高表达。在这里，我们为 ARG 筛选了所有完整的细菌 RefSeq 基因组。针对 IS 元件、整合子、质粒和系统发育分散研究检测到的 ARG 的遗传背景。提出了 ARG-MOB 量表，它表明检测到的 ARG 在细菌基因组中的移动程度。抗生素外排基因很少被动员，因此得出的结论是，这些基因通常是看家基因，不会通过过度表达来赋予抗性。在 15,790 个研究的基因组中，甚至 80% 的 β-内酰胺酶从未或很少被动员。然而，一些 ARG 确实被动员并与 IS 元件、质粒和整合子共存。这些结果对筛选抗性决定因素的研究的设计和解释具有影响，因为动员的 ARG 对人类健康构成了更具体的风险，尤其是在异源表达下，与仅在克隆实验中显示赋予抗性的 ARG 组相比。

       The degree to which antibiotic resistance genes (ARGs) are mobilized by insertion sequence (IS) elements, plasmids, and integrons has a strong association with their likelihood to function as resistance determinants. This stems from genetic decontextualization where strong promoters often present in IS elements and integrons and the copy number effect of plasmids contribute to high expression of accessory genes. 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. Antibiotic efflux genes are rarely mobilized and it is concluded that these are often housekeeping genes that are not decontextualized to confer resistance through overexpression. 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. 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, especially under heterologous expression, than groups of ARGs that have only been shown to confer resistance in cloning experiments.

https://www.biorxiv.org/content/10.1101/2021.01.10.426126v1.abstract