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、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尤其如此，包括本项目中用作模型的金黄色葡萄球菌，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，了解细菌水平基因转移对于确定毒性克隆如何出现和传播至关重要，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。我们支持这一建议的结果表明，我们目前对临床相关金黄色葡萄球菌致病性岛（SaPIs）如何被动员的理解范围极其狭窄，并且我们低估了SaPIs作为亚细胞生物的力量。我们在这里描述了sapi的一个子集已经进化出一种有趣的策略，通过盗版其他sapi来促进它们的高转移。这种优雅的策略允许通用内部和通用之间的SaPI传输。在这个项目中，我们将为这一前所未有的策略建立分子基础。为了实现这一目标，我们将在细菌进化和毒力中建立涉及致病性岛的新范式。

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.