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

建立细菌进化的新范式：通过横向转导实现染色体过度运动

• 批准号: EP/X026671/1
• 负责人: Jose R Penades
• 金额: $ 274.51万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX026671%2F1
• 关键词: Establishing; new; paradigm; bacterial; evolution

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 Importantly, two recent unpublished discoveries from the lab highlight the existence of additional mechanisms of gene transfer, related to LT, which require investigation.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.

噬菌体介导的基因转移是主要的进化力量。它通过两种明确描述的机制发生：广义转导和专门转导。我们发现金黄色葡萄球菌 pac 噬菌体参与横向转导 (LT)，这是迄今为止描述的最强大的转导模式。 LT 将细菌染色体的大部分区域转化为“超级移动平台”，以便在其边界内高频转移任何遗传元件。细菌 DNA 的转移频率高得惊人，比任何已知的转导机制至少高 1,000 倍。观察到的染色体 DNA 转移效率是前所未有的，代表了噬菌体生物学和移动遗传元件定义的范式转变。重要的是，实验室最近未发表的两项发现强调了与 LT 相关的其他基因转移机制的存在，这需要研究。尽管假设 cos 噬菌体不能转导 DNA，但我们的结果表明它们参与了一种新形式的 LT，我们称之为 cos-LT。我们还发现一大家族致病性岛，即噬菌体诱导染色体岛（PICI），通过称为 PICI-LT 的相关转导机制促进染色体基因的转移。重要的是，PICI-LT 具有独特的机制特征，表明它可能比 LT 更频繁、更强大。在这里，通过分析选定的不同主要病原体，我们将研究这些突破性的基因转移策略（LT、PICI-LT 和 cos-LT）在自然界中的广泛程度，以及它们对细菌基因组结构的影响，以及它们对细菌基因组结构的影响。毒力和抗菌素耐药性的演变。此外，细菌群落中 LT、PICI-LT 和 cos-LT 的环境驱动因素将在不同生态栖息地的模型中进行研究。拟议的研究需要对噬菌体和 PICI 对细菌进化影响的理解进行重大修改。

项目成果

Dual pathogenicity island transfer by piggybacking lateral transduction.

通过侧向转导进行双致病性岛转移。

• DOI: http://dx.10.1016/j.cell.2023.07.001
• 发表时间: 2023
• 期刊: Cell
• 影响因子: 64.5
• 作者: Chee MSJ

Characterisation of a Unique Repression System Present in Arbitrium Phages

Arbitrium 噬菌体中存在的独特抑制系统的表征

• DOI: http://dx.10.2139/ssrn.4412614
• 发表时间: 2023
• 作者: Brady A