Helper and satellite pathogenicity islands: the discovery of two novel subcellular elements with a huge impact on bacterial pathogenesis and evolution

近几十年来，大多数病原体的传染性越来越强，毒力越来越强，对抗生素的抗药性也越来越强。这意味着一种相当动态的进化能力，代表了基因组可塑性的显著水平，很可能是由水平基因转移(HGT)维持的。HGT可以在一个步骤内将良性细菌转化为毒力强的病原体。对于几种臭名昭著的病原体来说尤其如此，包括本项目中使用的金黄色葡萄球菌，对于这种病原体，噬菌体介导的HGT使相对良性的菌株能够引起致命的感染。因此，了解细菌的水平基因转移对于确定毒力克隆是如何出现和传播至关重要的，特别是在全球抗生素危机的背景下。噬菌体和致病性岛构成了更广泛的水平转移图的关键组成部分。我们支持这一提议的结果表明，我们目前对临床上相关的金黄色葡萄球菌致病岛(SaPI)如何被动员的理解范围极其狭窄，我们低估了SaPI作为亚细胞生物的力量。我们在这里描述了SAPI的一个子集已经发展出一种耐人寻味的战略，通过盗版其他SAPI来促进它们的高转移。这一优雅的策略允许在类内和类间进行SAPI传输。在这个项目中，我们将建立这一史无前例的战略的分子基础。为了实现这一目标，我们将建立新的范例，涉及细菌进化中的致病岛和毒力。

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, used in this project as model, for which phage-mediated HGT enables relatively benign strains to cause lethal infections. Consequently, understanding bacterial horizontal gene transfer is vital to establishing how virulent clones emerge and disseminate, especially in the context of the global antibiotic crisis. Phages and pathogenicity islands make up a key component of the wider horizontal transfer map. Our results in support of this proposal have demonstrated that our current understanding of how the clinically relevant S. aureus pathogenicity islands (SaPIs) can be mobilised are extremely narrow in scope, and that we have underestimated the power of SaPIs as subcellular organisms. We describe here that a subset of SaPIs has evolved an intriguing strategy that promotes their high transfer by pirating other SaPIs. This elegant strategy allows intra- and inter-generic SaPI transfer. In this project, we will establish the molecular bases of this unprecedented strategy. Achieving this objective we will establish novel paradigms involving pathogenicity islands in bacterial evolution and virulence.