The defective prophage pool of Escherichia coli O157: prophage-prophage interactions potentiate horizontal transfer of virulence determinants.

The defective prophage pool of Escherichia coli O157: prophage-prophage interactions potentiate horizontal transfer of virulence determinants.
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DOI:
10.1371/journal.ppat.1000408
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发表时间:
2009-05
期刊:
影响因子:
6.7
通讯作者:
Hayashi T
Hayashi T
中科院分区:
医学1区
文献类型:
--
作者:
Asadulghani M;Ogura Y;Ooka T;Itoh T;Sawaguchi A;Iguchi A;Nakayama K;Hayashi T

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噬菌体是促进细菌之间水平基因转移(HGT)的主要遗传因素。许多已测序的细菌基因组含有携带多种基因的多个原噬菌体,这一事实日益凸显了它们在动态细菌基因组进化中的作用。肠出血性大肠杆菌 O157 是最引人注目的病例。已测序的菌株 (O157 Sakai) 拥有 18 个原噬菌体 (Sp1–Sp18),编码许多与 O157 毒力相关的基因,包括两种强效细胞毒素志贺毒素 (Stx) 1 和 2 的基因。然而,大多数这些原噬菌体似乎包含多种遗传缺陷。为了了解这些有缺陷的前噬菌体是否有可能作为移动遗传元件来传播毒力决定子,我们仔细观察了 Sp1-Sp18 序列,定义了每个 Sp 的遗传缺陷,然后系统地分析了所有 Sp 的生物活性。我们发现许多有缺陷的前噬菌体,包括 Stx1 噬菌体,都是可诱导的,并以颗粒 DNA 的形式从 O157 细胞中释放。事实上,一些原噬菌体甚至可以转移到其他大肠杆菌菌株中。我们还表明,新的 Stx1 噬菌体是通过 Stx1 和 Stx2 噬菌体基因组之间的重组产生的。结果表明,这些有缺陷的原噬菌体不仅仅是O157进化过程中产生的遗传残余物,而是具有向其他细菌传播毒力相关基因和其他遗传性状的高潜力的遗传元件。我们推测 O157 原噬菌体池中的重组和各种其他类型的原噬菌体间相互作用增强了此类活性。我们的数据为嵌入细菌基因组中的缺陷原噬菌体的潜在活性提供了新的见解,并导致了缺陷原噬菌体群落中原噬菌体间相互作用的新概念的形成。细菌病毒,称为噬菌体或噬菌体,是促进细菌之间水平基因转移(HGT)的主要因素,由于发现许多已测序的细菌基因组含有多个携带多种基因(包括与毒力相关的基因)的原噬菌体,这种活性引发了新的兴趣。然而,从基因组序列中鉴定出的原噬菌体往往含有各种遗传缺陷,因此它们被认为仅仅是遗传遗迹,而没有注意到它们作为移动遗传元件的潜在活性。肠出血性大肠杆菌 O157 是最引人注目的例子,它含有多达 18 个原噬菌体。 O157原噬菌体携带大量与O157毒力相关的基因,但大多数具有多种遗传缺陷。在这项研究中,我们分析了 O157 前噬菌体的功能,并报告说,许多明显有缺陷的前噬菌体是可诱导的,并以颗粒 DNA 的形式从 O157 细胞中释放,其中一些可以转移到其他大肠杆菌菌株中。因此,我们应该认为这些前噬菌体具有传播毒力决定因素的巨大潜力。我们的结果进一步表明,它们作为移动遗传元件的活动通过原噬菌体之间各种类型的相互作用得到增强,从而在有缺陷的原噬菌体群落中制定了原噬菌体间相互作用的新概念。
Bacteriophages are major genetic factors promoting horizontal gene transfer (HGT) between bacteria. Their roles in dynamic bacterial genome evolution have been increasingly highlighted by the fact that many sequenced bacterial genomes contain multiple prophages carrying a wide range of genes. Enterohemorrhagic Escherichia coli O157 is the most striking case. A sequenced strain (O157 Sakai) possesses 18 prophages (Sp1–Sp18) that encode numerous genes related to O157 virulence, including those for two potent cytotoxins, Shiga toxins (Stx) 1 and 2. However, most of these prophages appeared to contain multiple genetic defects. To understand whether these defective prophages have the potential to act as mobile genetic elements to spread virulence determinants, we looked closely at the Sp1–Sp18 sequences, defined the genetic defects of each Sp, and then systematically analyzed all Sps for their biological activities. We show that many of the defective prophages, including the Stx1 phage, are inducible and released from O157 cells as particulate DNA. In fact, some prophages can even be transferred to other E. coli strains. We also show that new Stx1 phages are generated by recombination between the Stx1 and Stx2 phage genomes. The results indicate that these defective prophages are not simply genetic remnants generated in the course of O157 evolution, but rather genetic elements with a high potential for disseminating virulence-related genes and other genetic traits to other bacteria. We speculate that recombination and various other types of inter-prophage interactions in the O157 prophage pool potentiate such activities. Our data provide new insights into the potential activities of the defective prophages embedded in bacterial genomes and lead to the formulation of a novel concept of inter-prophage interactions in defective prophage communities. Bacterial viruses, known as bacteriophages or phages, are major factors promoting horizontal gene transfer (HGT) between bacteria, and this activity has sparked new interest in light of the discovery that many sequenced bacterial genomes harbor multiple prophages carrying a wide range of genes, including those related to virulence. However, prophages identified from genome sequences often contain various genetic defects, and they have therefore been regarded as merely genetic vestiges, with no attention paid to their potential activities as mobile genetic elements. Enterohemorraghic Escherichia coli O157, which harbors as many as 18 prophages, is the most striking such example. The O157 prophages carry numerous genes related to O157 virulence, but most possess multiple genetic defects. In this study, we analyze the functionalities of O157 prophages and report that many of the apparently defective prophages are inducible and released from the O157 cells as particulate DNA and that some can be transferred to other E. coli strains. We should therefore regard these prophages as having high potential to disseminate virulence determinants. Our results further suggest that their activities as mobile genetic elements are potentiated by various types of interactions among the prophages, formulating a novel concept of inter-prophage interactions in defective prophage communities.
DOI: 10.1016/j.virol.2004.01.016
发表时间: 2004-04-25
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