Yao Yi, Maddamsetti Rohan, Weiss Andrea, Ha Yuanchi, Wang Teng, Wang Shangying, You Lingchong
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA.
Nat Ecol Evol. 2022 May;6(5):555-564. doi: 10.1038/s41559-022-01705-2. Epub 2022 Mar 28.
The spread of genes encoding antibiotic resistance is often mediated by horizontal gene transfer (HGT). Many of these genes are associated with transposons, a type of mobile genetic element that can translocate between the chromosome and plasmids. It is widely accepted that the translocation of antibiotic resistance genes onto plasmids potentiates their spread by HGT. However, it is unclear how this process is modulated by environmental factors, especially antibiotic treatment. To address this issue, we asked whether antibiotic exposure would select for the transposition of resistance genes from chromosomes onto plasmids and, if so, whether antibiotic concentration could tune the distribution of resistance genes between chromosomes and plasmids. We addressed these questions by analysing the transposition dynamics of synthetic and natural transposons that encode resistance to different antibiotics. We found that stronger antibiotic selection leads to a higher fraction of cells carrying the resistance on plasmids because the increased copy number of resistance genes on multicopy plasmids leads to higher expression of those genes and thus higher cell survival when facing antibiotic selection. Once they have transposed to plasmids, antibiotic resistance genes are primed for rapid spread by HGT. Our results provide quantitative evidence for a mechanism by which antibiotic selection accelerates the spread of antibiotic resistance in microbial communities.
编码抗生素抗性的基因传播通常由水平基因转移（HGT）介导。其中许多基因与转座子相关，转座子是一种可在染色体和质粒之间易位的移动遗传元件。人们普遍认为，抗生素抗性基因向质粒的易位通过水平基因转移增强了它们的传播。然而，目前尚不清楚这一过程如何受到环境因素的调节，尤其是抗生素治疗的影响。为了解决这个问题，我们研究了抗生素暴露是否会促使抗性基因从染色体转座到质粒上，如果是这样，抗生素浓度是否能够调节抗性基因在染色体和质粒之间的分布。我们通过分析编码对不同抗生素抗性的合成和天然转座子的转座动力学来解决这些问题。我们发现，更强的抗生素选择导致携带质粒上抗性的细胞比例更高，因为多拷贝质粒上抗性基因拷贝数的增加导致这些基因的更高表达，从而在面对抗生素选择时细胞存活率更高。一旦它们转座到质粒上，抗生素抗性基因就为通过水平基因转移快速传播做好了准备。我们的结果为抗生素选择加速微生物群落中抗生素抗性传播的机制提供了定量证据。
