Transcriptomic and Metabolomics Profiling of Phage-Host Interactions between Phage PaP1 and Pseudomonas aeruginosa.
Transcriptomic and Metabolomics Profiling of Phage-Host Interactions between Phage PaP1 and Pseudomonas aeruginosa.
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噬菌体 PaP1 和铜绿假单胞菌之间噬菌体-宿主相互作用的转录组学和代谢组学分析。
DOI：
10.3389/fmicb.2017.00548
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发表时间：
2017
影响因子：
5.2
通讯作者：
Le S
中科院分区：
文献类型：
--
作者：
Zhao X;Shen M;Jiang X;Shen W;Zhong Q;Yang Y;Tan Y;Agnello M;He X;Hu F;Le S
由于对噬菌体治疗潜力的重新关注，噬菌体-宿主相互作用的基本生物学引起了越来越多的关注。此外，了解被噬菌体抑制的宿主途径可能为新的药物靶点提供线索。然而，噬菌体对细菌基因表达和代谢的影响仍然知之甚少。在这项研究中，我们通过结合转录组学和代谢组学分析来追踪噬菌体与宿主的相互作用，这些相互作用是由一种溶解噬菌体PaP1感染的铜绿假单胞菌引起的。与未感染的宿主相比，噬菌体感染宿主的差异表达基因（deg）占7.1% (399/5655)；其中354个基因在感染后期下调。在氨基酸和能量代谢途径中发现了许多下调的deg。利用代谢组学方法，我们分析了与未感染对照相比，感染pap1的宿主体内代谢物水平的变化。感染PaP1后，宿主胸腺嘧啶显著增加，这一结果进一步得到了PaP1编码胸腺嘧啶合成酶基因表达增加的支持。此外，细胞内甜菜碱浓度急剧降低，而胆碱浓度升高，可能是由于胆碱-甘氨酸甜菜碱途径的下调。有趣的是，胆碱-甘氨酸甜菜碱途径是一个潜在的抗菌靶点；先前的研究表明，抑制betB导致甜菜碱的消耗和甜菜碱醛的积累，两者的结合对铜绿假单胞菌具有毒性。这些结果详细描述了铜绿假单胞菌中噬菌体定向代谢的一个例子。噬菌体编码的辅助代谢基因和噬菌体导向的宿主基因表达都可能导致宿主体内观察到的代谢变化。
The basic biology of bacteriophage–host interactions has attracted increasing attention due to a renewed interest in the therapeutic potential of bacteriophages. In addition, knowledge of the host pathways inhibited by phage may provide clues to novel drug targets. However, the effect of phage on bacterial gene expression and metabolism is still poorly understood. In this study, we tracked phage–host interactions by combining transcriptomic and metabolomic analyses in Pseudomonas aeruginosa infected with a lytic bacteriophage, PaP1. Compared with the uninfected host, 7.1% (399/5655) of the genes of the phage-infected host were differentially expressed genes (DEGs); of those, 354 DEGs were downregulated at the late infection phase. Many of the downregulated DEGs were found in amino acid and energy metabolism pathways. Using metabolomics approach, we then analyzed the changes in metabolite levels in the PaP1-infected host compared to un-infected controls. Thymidine was significantly increased in the host after PaP1 infection, results that were further supported by increased expression of a PaP1-encoded thymidylate synthase gene. Furthermore, the intracellular betaine concentration was drastically reduced, whereas choline increased, presumably due to downregulation of the choline–glycine betaine pathway. Interestingly, the choline–glycine betaine pathway is a potential antimicrobial target; previous studies have shown that betB inhibition results in the depletion of betaine and the accumulation of betaine aldehyde, the combination of which is toxic to P. aeruginosa. These results present a detailed description of an example of phage-directed metabolism in P. aeruginosa. Both phage-encoded auxiliary metabolic genes and phage-directed host gene expression may contribute to the metabolic changes observed in the host.