Preferential Cellular Accumulation of ppGpp or pppGpp in<i>Escherichia Coli</i>

Potrykus, Katarzyna; Cashel, Michael

doi:10.1002/9781119004813.ch44

Cited by 4 publications

(4 citation statements)

References 45 publications

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“…It is almost certain that the 3’diphosphate plays a crucial role here since GTP and GDP do not display such regulatory effects. The nucleotide’s 5’ moiety also plays a role, as pppGpp and ppGpp were shown to affect the E. coli transcription to a different extent, with ppGpp being more potent than pppGpp [17; 18]. Indeed, guanosine pentaphosphate phosphatase (GppA) exists in E. coli , whose presence can be viewed as a means of fine tuning regulation.…”

Section: Introductionmentioning

confidence: 99%

Structure-function comparisons of (p)ppApp vs (p)ppGpp for Escherichia coli RNA polymerase binding sites and for rrnB P1 promoter regulatory responses in vitro

Bruhn-Olszewska

Molodtsov

Sobala

et al. 2018

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Precise regulation of gene expression is crucial for bacteria to respond to changing environmental conditions. In addition to protein factors affecting RNA polymerase (RNAP) activity, second messengers play an important role in transcription regulation, such as well-known effectors of the stringent response: guanosine 5'triphosphate-3'diphosphate and guanosine 3', 5'-bis(diphosphate) [(p)ppGpp]. Although much is known about importance of the 5' and 3' moieties of (p)ppGpp, the role of the guanine base remains somewhat cryptic. Here, we use (p)ppGpp's adenine analogs [(p)ppApp] to investigate how the nucleobase contributes to determine its binding site and transcriptional regulation. We determined X-ray crystal structure of Escherichia coli RNAP-(p)ppApp complex, which shows the analogs bind near the active site and switch regions of RNAP. We have also explored the regulatory effects of (p)ppApp on transcription initiating from the well-studied E. coli rrnB P1 promoter to assess and compare properties of (p)ppApp with (p)ppGpp. We demonstrate that contrary to (p)ppGpp, (p)ppApp activates transcription at this promoter and DksA hinders this effect. Moreover, pppApp exerts a stronger effect than ppApp. We also show that when ppGpp and pppApp are present together, the outcome depends on which one of them was pre-incubated with RNAP first. This behavior suggests a surprising Yin-Yang like reciprocal plasticity of RNAP responses at a single promoter, occasioned simply by pre-exposure to one or the other nucleotide. Our observations underscore the importance of the (p)ppNpp's purine nucleobase for interactions with RNAP, which may lead to a better fundamental understanding of (p)ppGpp regulation of RNAP activity.

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Section: Introductionmentioning

confidence: 99%

Structure-function comparisons of (p)ppApp vs (p)ppGpp for Escherichia coli RNA polymerase binding sites and for rrnB P1 promoter regulatory responses in vitro

Bruhn-Olszewska

Molodtsov

Sobala

et al. 2018

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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“…A). During amino acid starvation, the (p)ppGpp nucleotides are accumulated, reaching levels nearly equal to that of GTP . Accumulation of (p)ppGpp affects bacterial cell growth and general metabolism by the alarmones bound directly to RNA polymerase as well as the enzymes involved in nucleotide synthesis and uptake .…”

Section: Introductionmentioning

confidence: 99%

“…Intriguingly, the regulatory activities of pppGpp and ppGpp are different; ppGpp is more potent than pppGpp with respect to the regulation of cell growth rate, RNA/DNA ratio, ribosomal RNA synthesis, and transcription initiation . Rapid conversion of pppGpp to ppGpp is specifically catalyzed by pppGpp phosphohydrolase (GppA), encoded by the gppA gene in Escherichia coli .…”

Section: Introductionmentioning

confidence: 99%

Structure and activity of PPX/GppA homologs from Escherichia coli and Helicobacter pylori

Dharmasena

Wang

et al. 2019

The FEBS Journal

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Rapid adaptation to environmental changes is crucial for bacterial survival. Almost all bacteria possess a conserved stringent response system to prompt transcriptional and metabolic responses toward stress. The adaptive process relies on alarmones, guanosine pentaphosphate (pppGpp), and tetraphosphate (ppGpp), to regulate global gene expression. The ppGpp is more potent than pppGpp in the regulatory activity, and pppGpp phosphohydrolase (GppA) plays a key role in (p)ppGpp homeostasis. Sharing a similar domain structure, GppA is indistinguishable from exopolyphosphatase (PPX), which mediates the metabolism of cellular inorganic polyphosphate. Here, our phylogenetic analysis of PPX/GppA homologs in bacteria shows a wide distribution with several distinct subfamilies, and our structural and functional analysis of Escherichia coli GppA and Helicobacter pylori PPX/GppA reveals unique properties of each homolog. These results explain how each homolog possesses its distinct functionality.

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“…This ability is related to functioning of specific regulatory networks that change the metabolism of the cells and make them resistant [3]. Well-known components of these networks are bacterial alarmone (p)ppGpp synthesized by RelA or SpoT and stress-induced sigma factor RpoS [4, 5]. These components largely reprogram gene expression that is crucial for survival and formation of so-called cross-protection when one stress factor forms the general resistance to multiple ones.…”

Section: Introductionmentioning

confidence: 99%

Global Gene Expression Analysis of Cross-Protected Phenotype of Pectobacterium atrosepticum

et al. 2017

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The ability to adapt to adverse conditions permits many bacterial species to be virtually ubiquitous and survive in a variety of ecological niches. This ability is of particular importance for many plant pathogenic bacteria that should be able to exist, except for their host plants, in different environments e.g. soil, water, insect-vectors etc. Under some of these conditions, bacteria encounter absence of nutrients and persist, acquiring new properties related to resistance to a variety of stress factors (cross-protection). Although many studies describe the phenomenon of cross-protection and several regulatory components that induce the formation of resistant cells were elucidated, the global comparison of the physiology of cross-protected phenotype and growing cells has not been performed. In our study, we took advantage of RNA-Seq technology to gain better insights into the physiology of cross-protected cells on the example of a harmful phytopathogen, Pectobacterium atrosepticum (Pba) that causes crop losses all over the world. The success of this bacterium in plant colonization is related to both its virulence potential and ability to persist effectively under various stress conditions (including nutrient deprivation) retaining the ability to infect plants afterwards. In our previous studies, we showed Pba to be advanced in applying different adaptive strategies that led to manifestation of cell resistance to multiple stress factors. In the present study, we determined the period necessary for the formation of cross-protected Pba phenotype under starvation conditions, and compare the transcriptome profiles of non-adapted growing cells and of adapted cells after the cross-protective effect has reached the maximal level. The obtained data were verified using qRT-PCR. Genes that were expressed differentially (DEGs) in two cell types were classified into functional groups and categories using different approaches. As a result, we portrayed physiological features that distinguish cross-protected phenotype from the growing cells.

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Preferential Cellular Accumulation of ppGpp or pppGpp inEscherichia Coli

Cited by 4 publications

References 45 publications

Structure-function comparisons of (p)ppApp vs (p)ppGpp for Escherichia coli RNA polymerase binding sites and for rrnB P1 promoter regulatory responses in vitro

Structure-function comparisons of (p)ppApp vs (p)ppGpp for Escherichia coli RNA polymerase binding sites and for rrnB P1 promoter regulatory responses in vitro

Structure and activity of PPX/GppA homologs from Escherichia coli and Helicobacter pylori

Global Gene Expression Analysis of Cross-Protected Phenotype of Pectobacterium atrosepticum

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