Molecular biology of the PICIs, a novel and widespread family of mobile genetic elements involved in bacterial virulence

PICIs 的分子生物学，这是一个涉及细菌毒力的新型且广泛的移动遗传元件家族

• 批准号: MR/M003876/1
• 负责人: Jose R Penades
• 金额: $ 46.81万
• 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: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM003876%2F1
• 关键词: Molecular; biology; PICIs; novel; widespread

The idea that bacterial genomes within one single species can vary widely in gene content is not new. However, it was only with the advent of the genomic era that the phenomenon has been properly perceived. 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 20% consists of MGEs, which have moved freely within and between species and have occasionally crossed intergeneric boundaries. With 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 with host adaptation. Now, we hypothesise that similar elements occur widely in bacteria, conforming a unique class of mobile genetic elements, 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.The overall goal of this project is double: on one hand, we will try to confirm the existence of this novel and widespread family of mobile genetic elements, the PICIs. On the other hand, we will try to demonstrate that these elements have an important role in virulence by encoding novel and uncharacterised virulent genes. We propose that the successful completion of our research will introduce a new paradigm in the understanding of the biology of pathogenicity islands and therefore of bacterial evolution. Our studies will greatly enhance understanding of the evolution of pathogenic bacteria and apparition of novel virulence clones through the acquisition of MGEs, especially across genera.

同一物种内的细菌基因组在基因内容上可能存在很大差异，这并不是什么新鲜事。然而，只是随着基因组时代的到来，这一现象才得到适当的认识。不仅基因组大小不同;存在于来自特定物种的不同菌株中的大量基因甚至不相关，即在其他菌株中没有同源基因。这些基因大多携带在移动的遗传元件（MGE）上，包括质粒、噬菌体、致病岛、转座子或整合子，它们可以潜在地在细菌之间转移。因此，现在假设水平基因转移（HGT）在细菌进化中具有极其重要的作用。事实上，据估计，任何特定细菌物种的现存遗传内容的约20%是从其他生物体获得的。也许这20%中的一半由MGE组成，它们在物种内部和物种之间自由移动，偶尔会跨越属间界限。对于兼性病原体，MGEs主要负责抗生素耐药性，环境适应性和我们认为是致病机制的宿主组织中的各种各样的适应性。在大多数病原性细菌中，所有已知种类的细菌MGE都可能导致发病机制，并且特别引人注目的是，基本上所有引起特定毒素介导的疾病-毒素病-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、肉毒中毒、溶血性尿毒症综合征或坏死性筋膜炎的细菌毒素，由MGE编码。该应用程序代表了从2003年开始并延伸到现在的长期且高效的研究计划的高潮。在此期间，我们已经表征了一个新的移动的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，以及与宿主适应相关的其他毒力因子的来源。现在，我们假设类似的元件广泛存在于细菌中，符合一类独特的移动的遗传元件，噬菌体诱导的染色体岛（PICI）。我们认为PICI已经广泛地传播到整个细菌世界，并且比它们的宿主生物体分散得慢得多。如果这是真的，这些发现代表了一类新的MGE的发现，这对细菌世界中的横向基因转移和毒力具有广泛的影响。该项目的总体目标是双重的：一方面，我们将试图证实这种新颖且广泛的移动的遗传元件家族PICI的存在。另一方面，我们将试图证明，这些元素有一个重要的作用，通过编码新的和未表征的毒力基因的毒力。我们建议，我们的研究的成功完成将引入一个新的模式，在理解生物学的致病性岛，因此细菌的进化。我们的研究将大大提高理解的致病菌的进化和新的毒力克隆的出现，通过收购MGE，特别是跨属。

项目成果

Convergent evolution involving dimeric and trimeric dUTPases in pathogenicity island mobilization.

• DOI: 10.1371/journal.ppat.1006581
• 发表时间: 2017-09
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Donderis J;Bowring J;Maiques E;Ciges-Tomas JR;Alite C;Mehmedov I;Tormo-Mas MA;Penadés JR;Marina A
• 通讯作者: Marina A

Convergent evolution of pathogenicity islands in helper cos phage interference.

• DOI: 10.1098/rstb.2015.0505
• 发表时间: 2016-11-05
• 期刊: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
• 作者: Carpena N;Manning KA;Dokland T;Marina A;Penadés JR
• 通讯作者: Penadés JR

Pirating conserved phage mechanisms promotes promiscuous staphylococcal pathogenicity island transfer.

盗版保守的噬菌体机制促进了混杂的葡萄球菌致病岛转移。

• DOI: 10.7554/elife.26487
• 发表时间: 2017-08-08
• 期刊: eLife
• 影响因子: 7.7
• 作者: Bowring J;Neamah MM;Donderis J;Mir-Sanchis I;Alite C;Ciges-Tomas JR;Maiques E;Medmedov I;Marina A;Penadés JR
• 通讯作者: Penadés JR