MRC Centre for Molecular Bacteriology and Infection, Imperial College London, SW7 2AZ, UK.
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8TA, UK.
Nucleic Acids Res. 2022 Oct 28;50(19):11109-11127. doi: 10.1093/nar/gkac855.
Mobile genetic elements control their life cycles by the expression of a master repressor, whose function must be disabled to allow the spread of these elements in nature. Here, we describe an unprecedented repression-derepression mechanism involved in the transfer of Staphylococcus aureus pathogenicity islands (SaPIs). Contrary to the classical phage and SaPI repressors, which are dimers, the SaPI1 repressor StlSaPI1 presents a unique tetrameric conformation never seen before. Importantly, not just one but two tetramers are required for SaPI1 repression, which increases the novelty of the system. To derepress SaPI1, the phage-encoded protein Sri binds to and induces a conformational change in the DNA binding domains of StlSaPI1, preventing the binding of the repressor to its cognate StlSaPI1 sites. Finally, our findings demonstrate that this system is not exclusive to SaPI1 but widespread in nature. Overall, our results characterize a novel repression-induction system involved in the transfer of MGE-encoded virulence factors in nature.
移动遗传元件通过表达主阻遏物来控制其生命周期，为了允许这些元件在自然界中传播，必须使主阻遏物的功能失活。在这里，我们描述了一种在金黄色葡萄球菌毒力岛（SaPIs）转移中涉及的前所未有的阻遏-去阻遏机制。与经典的噬菌体和 SaPI 阻遏物不同，SaPI1 阻遏物 StlSaPI1 呈现出一种从未见过的独特四聚体构象。重要的是，SaPI1 的阻遏需要不止一个而是两个四聚体，这增加了该系统的新颖性。为了解除 SaPI1 的阻遏，噬菌体编码的蛋白 Sri 结合并诱导 StlSaPI1 的 DNA 结合结构域发生构象变化，从而阻止阻遏物与其同源 StlSaPI1 位点结合。最后，我们的研究结果表明，该系统并非 SaPI1 所特有，而是在自然界中广泛存在。总的来说，我们的研究结果描述了一种在自然状态下转移 MGE 编码的毒力因子中涉及的新型阻遏诱导系统。
