Department of Biosciences, Durham University, Stockton Road, Durham DH1 3LE, UK.
The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Edinburgh EH25 9RG, UK.
Nucleic Acids Res. 2022 May 20;50(9):5191-5207. doi: 10.1093/nar/gkac334.
Bacteria are under constant assault by bacteriophages and other mobile genetic elements. As a result, bacteria have evolved a multitude of systems that protect from attack. Genes encoding bacterial defence mechanisms can be clustered into 'defence islands', providing a potentially synergistic level of protection against a wider range of assailants. However, there is a comparative paucity of information on how expression of these defence systems is controlled. Here, we functionally characterize a transcriptional regulator, BrxR, encoded within a recently described phage defence island from a multidrug resistant plasmid of the emerging pathogen Escherichia fergusonii. Using a combination of reporters and electrophoretic mobility shift assays, we discovered that BrxR acts as a repressor. We present the structure of BrxR to 2.15 Å, the first structure of this family of transcription factors, and pinpoint a likely binding site for ligands within the WYL-domain. Bioinformatic analyses demonstrated that BrxR-family homologues are widespread amongst bacteria. About half (48%) of identified BrxR homologues were co-localized with a diverse array of known phage defence systems, either alone or clustered into defence islands. BrxR is a novel regulator that reveals a common mechanism for controlling the expression of the bacterial phage defence arsenal.
细菌不断受到噬菌体和其他移动遗传元件的攻击。因此，细菌进化出了多种保护自身免受攻击的系统。编码细菌防御机制的基因可以聚集在“防御岛上”，为抵御更广泛的攻击提供潜在的协同保护水平。然而，关于这些防御系统的表达是如何控制的信息相对较少。在这里，我们对一种新发现的来自多药耐药质粒的噬菌体防御岛中的转录调节因子 BrxR 进行了功能表征，该质粒来自新兴病原体弗格森埃希氏菌。通过组合报告基因和电泳迁移率变动分析，我们发现 BrxR 作为一种抑制物起作用。我们呈现了 BrxR 的结构，分辨率达到 2.15 Å，这是该家族转录因子的第一个结构，并确定了 WYL 结构域内可能的配体结合位点。生物信息学分析表明，BrxR 家族同源物在细菌中广泛存在。大约一半（48%）鉴定出的 BrxR 同源物与各种已知的噬菌体防御系统一起，要么单独存在，要么聚集在防御岛上。BrxR 是一种新的调节剂，揭示了控制细菌噬菌体防御武器库表达的共同机制。
