Bacteriophage crosstalk: coordination of prophage induction by trans-acting antirepressors.
Bacteriophage crosstalk: coordination of prophage induction by trans-acting antirepressors.
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DOI：
10.1371/journal.pgen.1002149
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发表时间：
2011-06
期刊：
影响因子：
4.5
通讯作者：
Bossi L
中科院分区：
文献类型：
--
作者：
Lemire S;Figueroa-Bossi N;Bossi L
许多种类的细菌在它们的基因组中都有多个前驱体。前驱体通常携带赋予细菌选择性优势的基因，通常是在宿主殖民期间。前驱噬菌体可以通过一种称为诱导的过程转化为传染性病毒，这与细菌毒力基因的传播有关。噬菌体诱导的范例，如噬菌体Lambda模型所设置的，看到了由RecA刺激的噬菌体抑制子的自我蛋白分解启动的过程。在这里，我们展示了在沙门氏菌基因组中发现的一个大的Lambdoid原噬菌体家族使用了另一种诱导策略。这些噬菌体的抑制子在诱导时不会被切割；相反，它们会被小的抗阻遏子蛋白结合而失活。复合体的形成会导致阻遏物从DNA上解离。抗阻遏子基因位于免疫区域之外，受LexA抑制子的直接控制，从而将原噬菌体诱导直接插入SOS反应中。Gifsy-1和Gifsy-3是沙门氏菌前驱体Gifsy-1和Gifsy-3的抗抑制物，它们都针对这两个噬菌体的抑制子Gfor和GfhR，尽管后者识别不同的操作位点，并且这两个噬菌体是异源免疫的。相反，Gifsy-2噬菌体抑制子GtgR对GFOA和GfhA不敏感，但可被无关Fels-1原噬菌体(FsoA)的抗抑制子失活。这一反应更加令人惊讶，因为FsoA受控于Fels-1抑制物，而不是LexA，并且在Fels-1诱导中没有明显的作用，Fels-1诱导是通过Lambda CI样的抑制物切割机制发生的。抗阻遏子识别非同源抑制子的能力允许在多发性溶源性菌株中协调诱导多个原噬菌体。对大量细菌基因组(包括DNA数据库中的大多数大肠杆菌基因组)中不可切割的gfor/gtgR同源物的鉴定表明，反抑制介导的诱导比以前认识的要普遍得多。许多感染细菌的病毒(噬菌体)可以直接将它们的DNA整合到细菌的染色体中。这种情况被称为溶原性，与细菌进化有关，因为它是导致外来DNA在自然界中掺入的主要途径之一。事实上，噬菌体经常携带逃脱溶源抑制的基因，从而有利于细菌。如果细菌遭受DNA损伤，这种共生关系可能会终止。由宿主的RecA蛋白介导的一种机制导致抑制、病毒DNA切除和复制的解除。这个过程被称为原噬菌体诱导，杀死宿主并导致病毒颗粒的释放。在这项工作中，我们分析了在沙门氏菌基因组中自然存在的一个大的原噬菌体家族中诱导的机制。我们发现，与研究最好的模型噬菌体不同，这些沙门氏菌噬菌体的抑制子不经历RecA介导的蛋白分解；相反，它们被小的抗抑制子蛋白结合而失活。我们证明了一些抗抑制物可以同时作用于同源和非同源抑制子，从而允许同时诱导给定菌株中的不同的前驱噬菌体。我们讨论的证据表明，抗阻遏子介导的原噬菌体诱导在细菌世界中相当普遍。
Many species of bacteria harbor multiple prophages in their genomes. Prophages often carry genes that confer a selective advantage to the bacterium, typically during host colonization. Prophages can convert to infectious viruses through a process known as induction, which is relevant to the spread of bacterial virulence genes. The paradigm of prophage induction, as set by the phage Lambda model, sees the process initiated by the RecA-stimulated self-proteolysis of the phage repressor. Here we show that a large family of lambdoid prophages found in Salmonella genomes employs an alternative induction strategy. The repressors of these phages are not cleaved upon induction; rather, they are inactivated by the binding of small antirepressor proteins. Formation of the complex causes the repressor to dissociate from DNA. The antirepressor genes lie outside the immunity region and are under direct control of the LexA repressor, thus plugging prophage induction directly into the SOS response. GfoA and GfhA, the antirepressors of Salmonella prophages Gifsy-1 and Gifsy-3, each target both of these phages' repressors, GfoR and GfhR, even though the latter proteins recognize different operator sites and the two phages are heteroimmune. In contrast, the Gifsy-2 phage repressor, GtgR, is insensitive to GfoA and GfhA, but is inactivated by an antirepressor from the unrelated Fels-1 prophage (FsoA). This response is all the more surprising as FsoA is under the control of the Fels-1 repressor, not LexA, and plays no apparent role in Fels-1 induction, which occurs via a Lambda CI-like repressor cleavage mechanism. The ability of antirepressors to recognize non-cognate repressors allows coordination of induction of multiple prophages in polylysogenic strains. Identification of non-cleavable gfoR/gtgR homologues in a large variety of bacterial genomes (including most Escherichia coli genomes in the DNA database) suggests that antirepression-mediated induction is far more common than previously recognized. Many viruses that infect bacteria (bacteriophages) can direct the integration of their DNA into the bacterial chromosome. This condition, known as lysogeny, is relevant to bacterial evolution, as it is one of the main pathways leading to the incorporation of foreign DNA in nature. Indeed, bacteriophages often carry genes that escape lysogenic repression and benefit the bacterium. This symbiotic association can come to an end if bacteria suffer DNA damage. A mechanism mediated by the host's RecA protein causes the relief of repression, viral DNA excision, and replication. This process, known as prophage induction, kills the host and results in the release of viral particles. In this work, we have analyzed the mechanism responsible for induction in a large family of prophages naturally present in the genomes of Salmonella bacteria. We found that, unlike in best-studied model phages, the repressors of these Salmonella phages do not undergo RecA-mediated proteolysis; rather, they are inactivated by the binding of small antirepressor proteins. We show that some antirepressors can act on both cognate and non-cognate repressors, allowing separate prophages within a given strain to be induced simultaneously. We discuss evidence suggesting that antirepressor-mediated prophage induction is quite common in the bacterial world.
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影响因子：
3.5
作者：
CHEREPANOV, PP;WACKERNAGEL, W
通讯作者：
WACKERNAGEL, W
影响因子：
3.6
作者：
Figueroa-Bossi, N;Uzzau, S;Bossi, L
通讯作者：
Bossi, L
影响因子：
3.2
作者：
FAUBLADIER, M;BOUCHE, JP
通讯作者：
BOUCHE, JP
DOI：
10.1073/pnas.76.12.6147
发表时间：
1979-01-01
影响因子：
11.1
作者：
LITTLE, JW;HARPER, JE
通讯作者：
HARPER, JE
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL