Switzer Amy, Evangelopoulos Dimitrios, Figueira Rita, de Carvalho Luiz Pedro S, Brown Daniel R, Wigneshweraraj Sivaramesh
1MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, SW7 2AZ, UK.
2Mycobacterial Metabolism and Antibiotic Research Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
Microbiology (Reading). 2018 Nov;164(11):1457-1470. doi: 10.1099/mic.0.000683. Epub 2018 Jun 29.
The initial adaptive transcriptional response to nitrogen (N) starvation in Escherichia coli involves large-scale alterations to the transcriptome mediated by the transcriptional activator, NtrC. One of these NtrC-activated genes is yeaG, which encodes a conserved bacterial kinase. Although it is known that YeaG is required for optimal survival under sustained N starvation, the molecular basis by which YeaG benefits N starved E. coli remains elusive. By combining transcriptomics with targeted metabolomics analyses, we demonstrate that the methionine biosynthesis pathway becomes transcriptionally dysregulated in ΔyeaG bacteria experiencing sustained N starvation. It appears the ability of MetJ, the master transcriptional repressor of methionine biosynthesis genes, to effectively repress transcription of genes under its control is compromised in ΔyeaG bacteria under sustained N starvation, resulting in transcriptional derepression of MetJ-regulated genes. Although the aberrant biosynthesis does not appear to be a contributing factor for the compromised viability of ΔyeaG bacteria experiencing sustained N starvation, this study identifies YeaG as a novel regulatory factor in E. coli affecting the transcription of methionine biosynthesis genes under sustained N starvation.
大肠杆菌对氮(N)饥饿的初始适应性转录反应涉及转录激活因子NtrC介导的转录组大规模改变。这些被NtrC激活的基因之一是yeaG,它编码一种保守的细菌激酶。虽然已知YeaG是持续氮饥饿条件下最佳存活所必需的,但YeaG使氮饥饿的大肠杆菌受益的分子基础仍然不清楚。通过将转录组学与靶向代谢组学分析相结合,我们证明在经历持续氮饥饿的ΔyeaG细菌中,甲硫氨酸生物合成途径的转录出现失调。在持续氮饥饿的ΔyeaG细菌中,甲硫氨酸生物合成基因的主要转录阻遏物MetJ有效阻遏其控制下基因转录的能力似乎受到损害,导致MetJ调控基因的转录去阻遏。虽然异常生物合成似乎不是经历持续氮饥饿的ΔyeaG细菌生存能力受损的一个促成因素,但本研究确定YeaG是大肠杆菌中一种新型调节因子,在持续氮饥饿条件下影响甲硫氨酸生物合成基因的转录。