Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198, Gif-sur-Yvette, France.
Graduate School of Structure and Dynamics of Living Systems, Université Paris-Saclay, 91190, Gif-sur-Yvette, France.
Nucleic Acids Res. 2023 Apr 11;51(6):2790-2799. doi: 10.1093/nar/gkad075.
Dissemination of antibiotic resistance, a current societal challenge, is often driven by horizontal gene transfer through bacterial conjugation. During conjugative plasmid transfer, single-stranded (ss) DNA is transferred from the donor to the recipient cell. Subsequently, a complete double-stranded (ds) plasmid molecule is generated and plasmid-encoded genes are expressed, allowing successful establishment of the transconjugant cell. Such dynamics of transmission can be modulated by host- or plasmid-encoded factors, either in the donor or in the recipient cell. We applied transposon insertion sequencing to identify host-encoded factors that affect conjugative transfer frequency in Escherichia coli. Disruption of the recipient uvrD gene decreased the acquisition frequency of conjugative plasmids belonging to different incompatibility groups. Results from various UvrD mutants suggested that dsDNA binding activity and interaction with RNA polymerase are dispensable, but ATPase activity is required for successful plasmid establishment of transconjugant cells. Live-cell microscopic imaging showed that the newly transferred ssDNA within a uvrD- recipient often failed to be converted to dsDNA. Our work suggested that in addition to its role in maintaining genome integrity, UvrD is also key for the establishment of horizontally acquired plasmid DNA that drives genome diversity and evolution.
抗生素耐药性的传播是当前面临的一个社会挑战,通常是由细菌接合导致的水平基因转移驱动的。在接合质粒转移过程中,单链 (ss) DNA 从供体转移到受体细胞。随后,会生成完整的双链 (ds) 质粒分子,并表达质粒编码的基因,从而使转导细胞成功建立。这种传递动力学可以通过供体或受体细胞中宿主或质粒编码的因素进行调节。我们应用转座子插入测序来鉴定影响大肠杆菌接合转移频率的宿主编码因素。破坏受体 uvrD 基因降低了不同不相容性群的接合质粒的获得频率。来自各种 UvrD 突变体的结果表明,dsDNA 结合活性和与 RNA 聚合酶的相互作用不是必需的,但 ATP 酶活性对于转导细胞中质粒的成功建立是必需的。活细胞显微镜成像显示,uvrD-受体中的新转移的 ssDNA 常常无法转化为 dsDNA。我们的工作表明,除了在维持基因组完整性方面的作用外,UvrD 对于建立驱动基因组多样性和进化的水平获得质粒 DNA 也是关键的。