Establishing a new paradigm in bacterial evolution: chromosomal hypermobility via lateral transduction

噬菌体介导的基因转移是一种主要的进化力量。它通过两种充分描述的机制发生：广义和专门的转导。我们已经发现金黄色葡萄球菌pac参与侧向转导（LT），这是迄今为止描述的最强大的转导模式。LT将细菌染色体的大区域转化为“超移动平台”，以便在其边界内高频转移任何遗传元件。细菌DNA以惊人的高频率转移，比任何已知的转导机制高至少1,000倍。观察到的染色体DNA转移的效率是前所未有的，代表了噬菌体生物学和移动的遗传元件定义的范式转变。重要的是，该实验室最近的两项未发表的发现强调了与LT相关的基因转移的其他机制的存在，这些机制需要研究。虽然假定cos β不能与DNA结合，但我们的研究结果表明，它们参与了一种新形式的LT，我们称之为cos-LT。我们还发现，一个大家族的致病岛，噬菌体诱导的染色体岛（PICI），通过一种相关的转导机制促进染色体基因的转移，称为PICI-LT。重要的是，PICI-LT具有独特的机制特征，这表明它可能比LT更频繁和更强大。在这里，分析选定的各种主要病原体，我们将调查这些突破性的基因转移策略有多普遍（LT、PICI-LT和cos-LT）在自然界中，沿着它们对细菌基因组的结构以及毒力和抗微生物剂抗性的进化的影响。此外，LT，PICI-LT和cos-LT细菌群落之间的环境驱动因素将在不同的生态栖息地的模型中进行检查。这项拟议中的研究将需要对我们对细菌进化的影响的理解进行重大修订。

Phage-mediated gene transfer is a major evolutionary force. It occurs by two well-described mechanisms: generalised and specialised transduction. We have discovered that Staphylococcus aureus pac phages engage in lateral transduction (LT), the most powerful mode of transduction described to date. LT converts large regions of the bacterial chromosome into "hypermobile platforms" for the high frequency transfer of any genetic element within their boundaries. Bacterial DNA is transferred at astonishingly high frequencies that are at least 1,000 times greater than any known mechanism of transduction. The observed efficiency of chromosomal DNA transfer is unprecedented, representing a paradigm shift in phage biology and in the definition of mobile genetic elements. Importantly, two recent unpublished discoveries from the lab highlight the existence of additional mechanisms of gene transfer, related to LT, which require investigation. Although it's assumed that cos phages can't transduce DNA, our results indicate that they engage in a new form of LT that we have called cos-LT. We have also discovered that a large family of pathogenicity islands, the phage-inducible chromosomal islands (PICIs), promote the transfer of chromosomal genes by a related mechanism of transduction termed PICI-LT. Importantly, PICI-LT has unique mechanistic features suggesting it may be even more frequent and powerful than LT. Here, analysing selected diverse major pathogens, we'll investigate how widespread these ground-breaking strategies of gene transfer (LT, PICI-LT and cos-LT) are in nature, along with their impact on the structure of bacterial genomes, and the evolution of virulence and antimicrobial resistance. Furthermore, the environmental drivers of LT, PICI-LT and cos-LT among bacterial communities will be examined in models of distinct ecological habitats. The proposed research will require a major revision of our understanding of the impact of phages and PICIs on bacterial evolution.