YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway of Escherichia coli.
YdfD, a Lysis Protein of the Qin Prophage, Is a Specific Inhibitor of the IspG-Catalyzed Step in the MEP Pathway of Escherichia coli.
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YdfD，Qin 原噬菌体的裂解蛋白，是大肠杆菌 MEP 途径中 IspG 催化步骤的特异性抑制剂
DOI：
10.3390/ijms23031560
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发表时间：
2022-01-29
影响因子：
5.6
通讯作者：
Jia Z
中科院分区：
文献类型：
--
作者：
Lu Z;Wang B;Qiu Z;Zhang R;Zheng J;Jia Z
细菌隐形原噬菌体(缺陷原噬菌体)基因在表达时会极大地影响宿主生理，如导致细胞生长停滞或裂解。许多噬菌体编码裂解蛋白来破坏细胞膜。作为天然抗生素，只有少数裂解靶蛋白被鉴定出来。YdfD是秦氏隐匿噬菌体的裂解基因，编码一个63个氨基酸的蛋白质，在大肠杆菌中的异位表达可迅速导致几乎完全的细胞裂解。细菌2-C-甲基-D-赤藓糖醇4-磷酸(MEP)途径负责合成维持细菌生长所必需的异戊二烯类化合物。在这项研究中，我们提供了证据，在体内和体外，YdfD可以与参与MEP途径的关键酶IspG相互作用。我们发现，完整的YdfD是与IspG相互作用才能发挥其裂解功能所必需的，并且在一定的应激条件下，YdfD的mRNA水平显著增加。关键是，通过ispG的过度表达或IspG酶催化产物甲基赤藓糖醇2，4-环二磷酸的互补，可以取消YdfD诱导的细胞裂解。我们认为，来自秦隐噬菌体的YdfD抑制IspG，阻断MEP途径，导致细胞膜和细胞壁的生物合成受损，最终导致细胞溶解。
Bacterial cryptic prophage (defective prophage) genes are known to drastically influence host physiology, such as causing cell growth arrest or lysis, upon expression. Many phages encode lytic proteins to destroy the cell envelope. As natural antibiotics, only a few lysis target proteins were identified. ydfD is a lytic gene from the Qin cryptic prophage that encodes a 63-amino-acid protein, the ectopic expression of which in Escherichia coli can cause nearly complete cell lysis rapidly. The bacterial 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is responsible for synthesizing the isoprenoids uniquely required for sustaining bacterial growth. In this study, we provide evidence that YdfD can interact with IspG, a key enzyme involved in the MEP pathway, both in vivo and in vitro. We show that intact YdfD is required for the interaction with IspG to perform its lysis function and that the mRNA levels of ydfD increase significantly under certain stress conditions. Crucially, the cell lysis induced by YdfD can be abolished by the overexpression of ispG or the complementation of the IspG enzyme catalysis product methylerythritol 2,4-cyclodiphosphate. We propose that YdfD from the Qin cryptic prophage inhibits IspG to block the MEP pathway, leading to a compromised cell membrane and cell wall biosynthesis and eventual cell lysis.
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影响因子：
14.9
作者：
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通讯作者：
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作者：
通讯作者：
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影响因子：
16.6
作者：
Blaskovich MAT;Hansford KA;Gong Y;Butler MS;Muldoon C;Huang JX;Ramu S;Silva AB;Cheng M;Kavanagh AM;Ziora Z;Premraj R;Lindahl F;Bradford TA;Lee JC;Karoli T;Pelingon R;Edwards DJ;Amado M;Elliott AG;Phetsang W;Daud NH;Deecke JE;Sidjabat HE;Ramaologa S;Zuegg J;Betley JR;Beevers APG;Smith RAG;Roberts JA;Paterson DL;Cooper MA
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