The molecule guanosine tetraphophosphate (ppGpp) is most commonly considered an alarmone produced during acute stress. However, ppGpp is also present at low concentrations during steady-state growth. Whether ppGpp controls the same cellular targets at both low and high concentrations remains an open question and is vital for understanding growth rate regulation. It is widely assumed that basal ppGpp concentrations vary inversely with growth rate, and that the main function of basal ppGpp is to regulate transcription of ribosomal RNA in response to environmental conditions. Unfortunately, studies to confirm this relationship and to define regulatory targets of basal ppGpp are limited by difficulties in quantifying basal ppGpp. In this Perspective we compare reported concentrations of basal ppGpp in E. coli and quantify ppGpp within several strains using a recently developed analytical method. We find that although the inverse correlation between ppGpp and growth rate is robust across strains and analytical methods, absolute ppGpp concentrations do not absolutely determine RNA synthesis rates. In addition, we investigated the consequences of two separate RNA polymerase mutations that each individually reduce (but do not abolish) sensitivity to ppGpp and find that the relationship between ppGpp, growth rate, and RNA content of single-site mutants remains unaffected. Both literature and our new data suggest that environmental conditions may be communicated to RNA polymerase via an additional regulator. We conclude that basal ppGpp is one of potentially several agents controlling ribosome abundance and DNA replication initiation, but that evidence for additional roles in controlling macromolecular synthesis requires further study.

鸟嘌呤四磷酸鸟苷（ppGpp）分子最常被认为是在急性应激过程中产生的警钟。但是，ppGpp在稳态生长期间也以低浓度存在。ppGpp是否在低浓度和高浓度下都能控制相同的细胞靶点仍是一个悬而未决的问题，对于理解生长速率调节至关重要。人们普遍认为，基础ppGpp的浓度与生长速度成反比，基础ppGpp的主要功能是响应环境条件调节核糖体RNA的转录。不幸的是，由于定量基础ppGpp的困难，确定这种关系并确定基础ppGpp的调控目标的研究受到限制。在此透视图中，我们比较了报告的基础ppGpp浓度大肠杆菌并使用最新开发的分析方法对几种菌株中的ppGpp进行定量。我们发现，尽管在菌株和分析方法中ppGpp和生长速率之间呈负相关，但绝对ppGpp浓度并不能绝对确定RNA的合成速率。此外，我们调查了两个单独的RNA聚合酶突变的后果，每个突变都会各自降低（但不会废除）对ppGpp的敏感性，并发现ppGpp，生长速度和单位点突变体RNA含量之间的关系仍然不受影响。文献和我们的新数据均表明，环境条件可能会通过其他调节剂传达给RNA聚合酶。我们得出结论，基础ppGpp是控制核糖体丰度和DNA复制起始的潜在几种药物之一，