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Understanding a novel mechanism involving pathogenicity islands in the transfer of unlinked chromosomal virulence genes.

了解一种涉及未连锁染色体毒力基因转移中致病性岛的新机制。

基本信息

批准号：
BB/N002873/1
负责人：
Jose R Penades
金额：
$ 80.25万
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：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FN002873%2F1
关键词：
Understanding novel mechanism involving pathogenicity

项目摘要

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 and Escherichia coli, used in this project as models, for which phage-mediated HGT enables relatively benign strains to cause lethal infections. However, in spite of their relevance, the mechanisms underlying transfer of MGEs and emergence of new bacterial virulent clones are far to be completely known. Here we report the existence of a hitherto unrecognized attribute of pathogenicity islands, namely their ability to contribute to the enhancement of their hosts' pathogenicity independently of their own direct role. We have found that throughout the host chromosome are scattered homologs of the Staphylococcal pathogenicty island (SaPI) pac site, which are recognised by the SaPI coded TerS, leading to the encapsidation and high frequency transfer of chromosomal segments downstream of these pseudo-pac sites. Since SaPIs are very common in staphylococci, and since they encode terminases with different sequence specificities, they are thus capable as a genre, of promoting the exchange of alleles and the acquisition of genes that are important for pathogen adaptation. Although pathogenicity islands can convert an innocuous organism into a deadly pathogen, this is based entirely upon the virulence genes that they carry. The ability of pathogenicity islands to contribute to the pathogenicity of their hosts by directing the transfer of unlinked virulence genes is unprecedented. We note finally, that SaPI-like elements are very widespread, especially among Gram-positive pathogens, and suspect that these may well be capable of the same behavior. Here we will try to decipher the molecular basis underlying this novel mechanism of SaPI-mediated horizontal gene transfer, as well as demonstrate its broad distribution and relevance in the bacterial world.

近几十年来，大多数病原体的传染性、毒性和对抗生素的耐药性逐渐增强。这意味着一种相当动态的进化能力，代表了一种显著水平的基因组可塑性，最有可能是通过水平基因转移（HGT）来维持的。HGT可以在一个简单的步骤中将良性细菌转化为致命的病原体。对于一些臭名昭著的病原体来说尤其如此，包括金黄色葡萄球菌和大肠杆菌，它们在这个项目中被用作模型，噬菌体介导的HGT使相对良性的菌株能够引起致命的感染。然而，尽管它们具有相关性，但MGEs转移和新细菌毒性克隆出现的机制尚不完全清楚。在这里，我们报告了迄今为止尚未认识到的致病性岛屿的存在，即它们独立于其自身的直接作用而有助于增强其宿主的致病性的能力。我们发现在整个宿主染色体上散布着葡萄球菌致病性岛（SaPI） pac位点的同源物，这些同源物被SaPI编码的ter识别，导致这些伪pac位点下游的染色体片段被封装和高频转移。由于sapi在葡萄球菌中非常常见，并且由于它们编码具有不同序列特异性的末端，因此它们能够作为一种类型，促进等位基因的交换和获得对病原体适应很重要的基因。虽然致病性岛屿可以将无害的生物体转化为致命的病原体，但这完全取决于它们携带的毒力基因。致病性岛屿通过引导非连锁毒力基因的转移来促进其宿主致病性的能力是前所未有的。最后，我们注意到，类sapi元素非常普遍，特别是在革兰氏阳性病原体中，并怀疑它们很可能具有相同的行为。在这里，我们将试图破译这种sapi介导的水平基因转移新机制的分子基础，并证明其在细菌世界中的广泛分布和相关性。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The arbitrium system controls prophage induction.

DOI：
10.1016/j.cub.2021.08.072
发表时间：
2021-11-22
期刊：
Current biology : CB
影响因子：
0
作者：
Brady A;Quiles-Puchalt N;Gallego Del Sol F;Zamora-Caballero S;Felipe-Ruíz A;Val-Calvo J;Meijer WJJ;Marina A;Penadés JR
通讯作者：
Penadés JR

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
影响因子：
0
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

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