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

近几十年来，大多数病原体的传染性越来越强、毒性越来越强、对抗生素的耐药性越来越强。这意味着一个相当动态的进化能力，代表了一个显着水平的基因组可塑性，最有可能保持水平基因转移（HGT）。HGT可以在一个步骤中将良性细菌转化为毒性病原体。这对于几种臭名昭著的病原体尤其如此，包括金黄色葡萄球菌和大肠杆菌，在该项目中用作模型，噬菌体介导的HGT使相对良性的菌株能够引起致命感染。然而，尽管它们的相关性，MGE的转移和新的细菌毒性克隆的出现的潜在机制还远未完全了解。在这里，我们报告存在一个迄今未被认识到的属性的致病性岛，即它们的能力，以促进其宿主的致病性独立于自己的直接作用。我们已经发现，在整个宿主染色体是分散的同源物的葡萄球菌致病性岛（SaPI）的pac网站，这是由SaPI编码的TerS识别，导致这些假pac网站下游的染色体片段的双糖苷化和高频率的转移。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酶，因此它们作为一种类型能够促进等位基因的交换和对病原体适应重要的基因的获得。虽然致病岛可以将无害的生物体转化为致命的病原体，但这完全基于它们携带的毒力基因。致病岛通过引导不连锁的毒力基因的转移来促进其宿主的致病性的能力是前所未有的。最后，我们注意到，类Sapi元件非常普遍，特别是在革兰氏阳性病原体中，并且怀疑这些病原体很可能具有相同的行为。在这里，我们将试图破译这种新的机制，SaPI介导的水平基因转移的分子基础，以及证明其在细菌世界的广泛分布和相关性。

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.