Interplay of the phages phi29 and SPP1 with the B. subtilis (p)ppGpp response

噬菌体 phi29 和 SPP1 与枯草芽孢杆菌 (p)ppGpp 响应的相互作用

• 批准号: 464366151
• 负责人: Professor Dr. Gert Bange
• 金额: --
• 依托单位: Zentrum für Synthetische Mikrobiologie (SYNMIKRO)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/464366151?language=en
• 关键词: Interplay; phages; phi29; SPP1; B.

In order to successfully replicate, phages strongly rely on the metabolism of their bacterial hosts. Bacteria tightly control all aspects of their metabolism via the conserved stringent response (SR) that relies on the second messengers (p)ppGpp. The (p)ppGpp nucleotides essentially control all levels of the bacterial metabolism, including nucleotide and amino acid metabolism, DNA replication, transcription and translation. Cellular (p)ppGpp levels are typically controlled by members of the RelA/SpoT homology (RSH) proteins, which synthesize and/or degrade (p)ppGpp. Therefore, one strategy enabling the productive and resource-intense phage replication should include a reprogramming of the SR, and thus the cellular (p)ppGpp levels. Specifically, we will study how the phages phi29 and SPP1 interfere with the (p)ppGpp metabolism of their host, the Gram-positive model organism Bacillus subtilis. Our preliminary work shows that the RSH-type enzyme Rel is relevant during phage infection, while the two other (p)ppGpp synthetases RelP and RelQ are not. Also, phage infection triggers the production of Nudix-type hydrolases, which might be involved in the reduction of the cellular (p)ppGpp pools during phage infection. Eventually, phages also harbor their own (p)ppGpp hydrolases, which will be subject of this proposal. Taken together, we will provide a mechanistic picture of how phages interfere with the host (p)ppGpp response in order to enable their successful reproduction.

为了成功复制，噬菌体强烈依赖细菌宿主的新陈代谢。细菌通过依赖第二信使 (p)ppGpp 的保守严格反应 (SR) 严格控制其代谢的各个方面。 (p)ppGpp 核苷酸本质上控制细菌代谢的所有水平，包括核苷酸和氨基酸代谢、DNA 复制、转录和翻译。细胞 (p)ppGpp 水平通常由合成和/或降解 (p)ppGpp 的 RelA/SpoT 同源 (RSH) 蛋白成员控制。因此，一种能够实现高效且资源密集型噬菌体复制的策略应包括对 SR 进行重编程，从而对细胞 (p)ppGpp 水平进行重编程。具体来说，我们将研究噬菌体 phi29 和 SPP1 如何干扰其宿主（革兰氏阳性模型生物枯草芽孢杆菌）的 (p)ppGpp 代谢。我们的初步工作表明，RSH 型酶 Rel 在噬菌体感染过程中相关，而其他两种 (p)ppGpp 合成酶 RelP 和 RelQ 则不然。此外，噬菌体感染会触发 Nudix 型水解酶的产生，这可能与噬菌体感染期间细胞 (p)ppGpp 库的减少有关。最终，噬菌体也拥有自己的 (p)ppGpp 水解酶，这将成为本提案的主题。 总之，我们将提供噬菌体如何干扰宿主 (p)ppGpp 反应以使其成功繁殖的机制图。