Deciphering Gram-negative phage-inducible chromosomal island strategies for spreading in nature

破译革兰氏阴性噬菌体诱导的染色体岛在自然中传播的策略

• 批准号: MR/S00940X/2
• 负责人: Jose R Penades
• 金额: $ 60.06万
• 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: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS00940X%2F2
• 关键词: Deciphering; Gram; negative; phage; inducible

The concept that bacterial genomes within a single species can vary widely in gene content is not new. However, it was only with the arrival of the genomic era that the phenomenon has been properly understood. Not only was the genome size different; a significant number of the genes present in different strains from a specific species were not even related i.e. had no homologous genes in the others. Most of these genes were carried on mobile genetics elements (MGEs), including plasmids, bacteriophages, pathogenicity islands, transposons or integrons, which can be potentially transferred among bacteria. Thus, it is now assumed that horizontal gene transfer (HGT) has had an extremely important role in bacterial evolution. Indeed it has been estimated that some 20% of the extant genetic content of any given bacterial species has been acquired from other organisms. Perhaps half of this consists of MGEs, which have moved freely within and between species, and have occasionally crossed intergeneric boundaries. In facultative pathogens, MGEs are largely responsible for antibiotic resistance, environmental adaptations and the wide variety of adaptations to life in host tissues that we perceive as pathogenesis. In most pathogenic bacteria, all known classes of bacterial MGEs may contribute to pathogenesis, and it is particularly striking that essentially all of the bacterial toxins that cause specific toxin-mediated diseases - toxinoses - such as PVL pneumonia, diphtheria, dysentery, toxic shock syndrome, food poisoning, necrotizing pneumonia, scalded skin syndrome, botulism, hemolytic-uremic syndrome or necrotizing fasciitis, are encoded by MGEs.This application represents the culmination of a long and highly productive research program starting in 2003 and extending to the present. During this time we have characterised a novel family of mobile staphylococcal pathogenicity islands, the SaPIs, which are the only source of several important superantigens, including toxic shock syndrome toxin-1 and enterotoxins B and C, as well as the source for other virulence factors related to host adaptation. Not surprisingly, these elements are not just confined to the Staphylococci, but are widespread within Gram-positive bacteria. Recently, we have also demonstrated that similar elements occur widely in Gram-negative bacteria, conforming a unique class of MGEs, the phage-inducible chromosomal islands (PICIs). We suggest that the PICIs have spread widely throughout the bacterial world, and have diverged much more slowly than their host organisms. If true, these findings represent the discovery of a new class of MGE, which have a broad impact on lateral gene transfer and virulence in the bacterial world.Although our previous studies have deciphered how the PICI elements present in the Gram-positive bacteria are induced and horizontally transferred, two main questions remain to be determined in the biology of the Gram-negative PICIs: i) how these elements sense the presence of their helper phages, and ii) how they hijack the phage machinery for their own specific packaging, blocking phage reproduction. To decipher these two processes is of vital importance to understand how these elements spread in nature. In this project we will answer these questions. By achieving these objectives we will establish new paradigms involving pathogenicity islands in bacterial evolution and virulence, and will provide strategies to block pathogenicity island dissemination and the emergence of novel bacterial virulent clones.

单一物种内的细菌基因组的基因内容可能存在很大差异的概念并不新鲜。然而，直到基因组时代的到来，这一现象才被正确理解。不仅基因组大小不同，而且基因组大小也不同。来自特定物种的不同菌株中存在的大量基因甚至不相关，即在其他菌株中没有同源基因。这些基因大多数都携带在移动遗传元件（MGE）上，包括质粒、噬菌体、致病岛、转座子或整合子，它们可以在细菌之间转移。因此，现在假设水平基因转移（HGT）在细菌进化中发挥着极其重要的作用。事实上，据估计，任何给定细菌物种的现有遗传内容约有 20% 是从其他生物体获得的。也许其中一半由 MGE 组成，它们在物种内部和物种之间自由移动，并且偶尔跨越属间界限。在兼性病原体中，MGE 在很大程度上负责抗生素耐药性、环境适应以及宿主组织对生命的各种适应，我们将其视为发病机制。在大多数致病细菌中，所有已知类别的细菌 MGE 都可能参与发病，特别引人注目的是，基本上所有引起特定毒素介导疾病（毒素病）的细菌毒素，例如 PVL 肺炎、白喉、痢疾、中毒性休克综合征、食物中毒、坏死性肺炎、烫伤皮肤综合征、肉毒杆菌中毒、溶血性尿毒症综合征或坏死性筋膜炎，均由 MGE 编码。该应用程序代表了这是从 2003 年开始一直延续至今的一项长期且富有成效的研究计划的顶峰。在此期间，我们鉴定了一个新的移动葡萄球菌致病岛家族 SaPI，它是几种重要超抗原的唯一来源，包括中毒性休克综合征毒素 1 和肠毒素 B 和 C，以及其他毒力因子的来源与宿主适应有关。毫不奇怪，这些元素不仅限于葡萄球菌，而且广泛存在于革兰氏阳性细菌中。最近，我们还证明类似的元素广泛存在于革兰氏阴性细菌中，符合一类独特的 MGE，即噬菌体诱导染色体岛 (PICI)。我们认为，PICI 已在整个细菌世界中广泛传播，并且其分化速度比其宿主生物体慢得多。如果属实，这些发现代表了一类新的 MGE 的发现，它对细菌世界中的横向基因转移和毒力具有广泛的影响。尽管我们之前的研究已经破译了革兰氏阳性菌中存在的 PICI 元件是如何被诱导的和水平转移，革兰氏阴性 PICIs 的生物学仍有两个主要问题有待确定：i）这些元件如何感知辅助噬菌体的存在，以及 ii）它们如何劫持噬菌体机器以实现自身特定的目的包装，阻断噬菌体繁殖。破译这两个过程对于理解这些元素如何在自然界中传播至关重要。在这个项目中我们将回答这些问题。通过实现这些目标，我们将建立涉及细菌进化和毒力中致病岛的新范式，并将提供阻止致病岛传播和新型细菌毒力克隆出现的策略。

项目成果

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

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

Characterization of a unique repression system present in arbitrium phages of the SPbeta family

SPbeta 家族任意噬菌体中存在的独特抑制系统的表征

• DOI: http://dx.10.1016/j.chom.2023.11.003
• 发表时间: 2023
• 期刊: Cell Host & Microbe
• 影响因子: 30.3
• 作者: Brady A

Molecular Basis of Lysis-Lysogeny Decisions in Gram-Positive Phages.

革兰氏阳性噬菌体裂解-溶源决定的分子基础。

• DOI: http://dx.10.1146/annurev-micro-033121-020757
• 发表时间: 2021
• 期刊: Annual review of microbiology
• 作者: Brady A

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