Hijacking the Hijackers: Escherichia coli Pathogenicity Islands Redirect Helper Phage Packaging for Their Own Benefit
Hijacking the Hijackers: Escherichia coli Pathogenicity Islands Redirect Helper Phage Packaging for Their Own Benefit
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DOI：
10.1016/j.molcel.2019.06.017
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发表时间：
2019-09-05
期刊：
影响因子：
16
通讯作者：
Penades, Jose R.
中科院分区：
文献类型：
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作者：
Fillol-Salom, Alfred;Bacarizo, Julio;Penades, Jose R.
噬菌体可诱导染色体岛(PICI)代表了一类新的、普遍存在的可移动遗传元件，对细菌的毒力有广泛的影响。尽管它们之间存在相关性，但革兰氏阴性杆菌是如何劫持噬菌体机器来进行特定包装的，以及它们是如何阻止噬菌体繁殖的，仍有待确定。利用遗传和结构分析，我们通过证明革兰氏阴性PICI编码一种同时执行这些过程的蛋白质来解开这个谜团。我们将这种蛋白质命名为RPP(用于重定向噬菌体包装)，它与噬菌体终止酶小亚基相互作用，形成一个异源复合体。这种复合体不能识别噬菌体DNA，阻止噬菌体包装，但特异性地与PICI基因组结合，促进PICI包装。我们的研究揭示了允许PICI在自然界传播的作用机制，为理解致病岛的生物学从而理解细菌病原体进化引入了一种新的范式。
Phage-inducible chromosomal islands (PICIs) represent a novel and universal class of mobile genetic elements, which have broad impact on bacterial virulence. In spite of their relevance, how the Gramnegative PICIs hijack the phage machinery for their own specific packaging and how they block phage reproduction remains to be determined. Using genetic and structural analyses, we solve the mystery here by showing that the Gram-negative PICIs encode a protein that simultaneously performs these processes. This protein, which we have named Rpp (for redirecting phage packaging), interacts with the phage terminase small subunit, forming a hetero-complex. This complex is unable to recognize the phage DNA, blocking phage packaging, but specifically binds to the PICI genome, promoting PICI packaging. Our studies reveal the mechanism of action that allows PICI dissemination in nature, introducing a new paradigm in the understanding of the biology of pathogenicity islands and therefore of bacterial pathogen evolution.