Helper and satellite pathogenicity islands: the discovery of two novel subcellular elements with a huge impact on bacterial pathogenesis and evolution

辅助致病岛和卫星致病岛：发现两种对细菌发病机制和进化具有巨大影响的新型亚细胞元件

• 批准号: BB/S003835/1
• 负责人: Jose R Penades
• 金额: $ 52.4万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FS003835%2F1
• 关键词: Helper; satellite; pathogenicity; islands; discovery

In recent decades, most pathogens have become progressively more contagious, more virulent and more resistant to antibiotics. This implies a rather dynamic evolutionary capability, representing a remarkable level of genomic plasticity, most probably maintained by horizontal gene transfer (HGT). HGT can, in a single step, transform a benign bacterium into a virulent pathogen. This is especially true for several notorious pathogens, including Staphylococcus aureus, used in this project as model, for which phage-mediated HGT enables relatively benign strains to cause lethal infections. Consequently, understanding bacterial horizontal gene transfer is vital to establishing how virulent clones emerge and disseminate, especially in the context of the global antibiotic crisis. Phages and pathogenicity islands make up a key component of the wider horizontal transfer map. Our results in support of this proposal have demonstrated that our current understanding of how the clinically relevant S. aureus pathogenicity islands (SaPIs) can be mobilised are extremely narrow in scope, and that we have underestimated the power of SaPIs as subcellular organisms. We describe here that a subset of SaPIs has evolved an intriguing strategy that promotes their high transfer by pirating other SaPIs. This elegant strategy allows intra- and inter-generic SaPI transfer. In this project, we will establish the molecular bases of this unprecedented strategy. Achieving this objective we will establish novel paradigms involving pathogenicity islands in bacterial evolution and virulence.

近几十年来，大多数病原体的传染性、毒性和抗生素耐药性逐渐增强。这意味着相当动态的进化能力，代表了显着水平的基因组可塑性，很可能是通过水平基因转移（HGT）来维持的。 HGT 可以一步将良性细菌转化为剧毒病原体。对于几种臭名昭著的病原体尤其如此，包括本项目中用作模型的金黄色葡萄球菌，噬菌体介导的 HGT 使相对良性的菌株能够引起致命的感染。因此，了解细菌水平基因转移对于确定有毒克隆如何出现和传播至关重要，特别是在全球抗生素危机的背景下。噬菌体和致病岛构成了更广泛的水平转移图谱的关键组成部分。我们支持这一提议的结果表明，我们目前对如何动员临床相关的金黄色葡萄球菌致病岛（SaPI）的理解范围极其狭窄，并且我们低估了 SaPI 作为亚细胞生物的力量。我们在此描述 SaPI 的一个子集已经发展出一种有趣的策略，通过盗版其他 SaPI 来促进其高转移。这种优雅的策略允许类内和类间 SaPI 传输。在这个项目中，我们将建立这一前所未有的策略的分子基础。为了实现这一目标，我们将建立涉及细菌进化和毒力中致病性岛的新范式。

项目成果

A multihost bacterial pathogen overcomes continuous population bottlenecks to adapt to new host species.

多宿主细菌病原体克服了持续的种群瓶颈以适应新的宿主物种。

• DOI: http://dx.10.1126/sciadv.aax0063
• 发表时间: 2019
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Bacigalupe R

Bacteriophages benefit from mobilizing pathogenicity islands encoding immune systems against competitors.

噬菌体受益于动员编码免疫系统的致病岛来对抗竞争者。

• DOI: http://dx.10.1016/j.cell.2022.07.014
• 发表时间: 2022
• 期刊: Cell
• 影响因子: 64.5
• 作者: Fillol

A widespread family of phage-inducible chromosomal islands only steals bacteriophage tails to spread in nature.

一个广泛存在的噬菌体诱导染色体岛家族仅窃取噬菌体尾巴以在自然界中传播。

• DOI: http://dx.10.1016/j.chom.2022.12.001
• 发表时间: 2023
• 期刊: Cell host & microbe
• 影响因子: 30.3
• 作者: Alqurainy N

The arbitrium system controls prophage induction.

仲裁系统控制原噬菌体的诱导。

• DOI: http://dx.10.1016/j.cub.2021.08.072
• 发表时间: 2021
• 期刊: CB
• 作者: Brady A

Beyond the CRISPR-Cas safeguard: PICI-encoded innate immune systems protect bacteria from bacteriophage predation.

超越 CRISPR-Cas 保护措施：PICI 编码的先天免疫系统可保护细菌免受噬菌体捕食。

• DOI: http://dx.10.1016/j.mib.2020.06.002
• 发表时间: 2020
• 期刊: Current opinion in microbiology
• 影响因子: 5.4
• 作者: Fillol