Xenogeneic modulation of the ClpCP protease of Bacillus subtilis by a phage-encoded adaptor-like protein
Xenogeneic modulation of the ClpCP protease of Bacillus subtilis by a phage-encoded adaptor-like protein
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DOI：
10.1074/jbc.ra119.010007
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发表时间：
2019-11-15
影响因子：
4.8
通讯作者：
Wigneshweraraj, Sivaramesh
中科院分区：
文献类型：
--
作者：
Mulvenna, Nancy;Hantke, Ingo;Wigneshweraraj, Sivaramesh
yyyyy与真核病毒和古细菌病毒一样，噬菌体利用宿主的细胞途径进行复制，噬菌体也进化出了改变细菌宿主代谢的策略。枯草芽孢杆菌的SPO 1噬菌体感染导致细胞过程的全面重塑，导致细菌细胞转化为噬菌体后代生产的工厂。SPO 1基因组中的一组26个基因，称为宿主接管模块，编码潜在的细胞毒性蛋白，特异性关闭细菌宿主中的各种过程，包括转录，DNA合成和细胞分裂。然而，SPO 1宿主接管模块的许多基因的性质和细菌靶标仍然难以捉摸。通过对SPO 1宿主接管模块编码的基因产物的系统分析，在此我们鉴定了八种减弱B的基因产物。枯草杆菌生长在减弱细菌生长的八种噬菌体基因产物中，一种称为Gp 53的25-kDa蛋白质显示与B的ClpCP蛋白酶的AAA+伴侣蛋白ClpC相互作用。枯草芽孢杆菌我们的研究结果进一步揭示，Gp 53是一种噬菌体编码的衔接子样蛋白，其调节ClpCP蛋白酶的活性以使有效的SPO 1噬菌体后代发育成为可能。总之，我们的研究结果表明，细菌ClpCP蛋白酶是由SPO 1噬菌体衍生因子的异种（dys）调节的靶点，并将Gp 53添加到靶向细菌蛋白质降解的抗菌产品列表中，因此可能具有开发新型抗菌剂的实用性。
yyyyy Like eukaryotic and archaeal viruses, which coopt the host's cellular pathways for their replication, bacteriophages have evolved strategies to alter the metabolism of their bacterial host. SPO1 bacteriophage infection of Bacillus subtilis results in comprehensive remodeling of cellular processes, leading to conversion of the bacterial cell into a factory for phage progeny production. A cluster of 26 genes in the SPO1 genome, called the host takeover module, encodes for potentially cytotoxic proteins that specifically shut down various processes in the bacterial host, including transcription, DNA synthesis, and cell division. However, the properties and bacterial targets of many genes of the SPO1 host takeover module remain elusive. Through a systematic analysis of gene products encoded by the SPO1 host takeover module, here we identified eight gene products that attenuated B. subtilis growth. Of the eight phage gene products that attenuated bacterial growth, a 25-kDa protein called Gp53 was shown to interact with the AAA+ chaperone protein ClpC of the ClpCP protease of B. subtilis. Our results further reveal that Gp53 is a phage-encoded adaptor-like protein that modulates the activity of the ClpCP protease to enable efficient SPO1 phage progeny development. In summary, our findings indicate that the bacterial ClpCP protease is the target of xenogeneic (dys)regulation by a SPO1 phage-derived factor and add Gp53 to the list of antibacterial products that target bacterial protein degradation and therefore may have utility for the development of novel antibacterial agents.