New horizons for (p)ppGpp in bacterial and plant physiology

Braeken, Kristien; Moris, Martine; Daniels, Ruth; Vanderleyden, Jozef; Michiels, Jan

doi:10.1016/j.tim.2005.11.006

Cited by 203 publications

(171 citation statements)

References 68 publications

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“…Many pathogens have evolved survival strategies triggered by (p)ppGpp (Braeken et al, 2006). For example, accumulation of (p)ppGpp in Salmonella appears to induce HilA expression, which in turn regulates expression of SPI 1 and SPI 2 virulence genes (Thompson et al, 2006;Song et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

RelA regulates virulence and intracellular survival of Francisella novicida

et al. 2009

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Analysis of the genome of Francisella tularensis has revealed few regulatory systems, and how the organism adapts to conditions in different niches is poorly understood. The stringent response is a global stress response mediated by (p)ppGpp. The enzyme RelA has been shown to be involved in generation of this signal molecule in a range of bacterial species. We investigated the effect of inactivation of the relA gene in Francisella by generating a mutant in Francisella novicida. Under amino acid starvation conditions, the relA mutant was defective for (p)ppGpp production. Characterization showed the mutant to grow similarly to the wild-type, except that it entered stationary phase later than wild-type cultures, resulting in higher cell yields. The relA mutant showed increased biofilm formation, which may be linked to the delay in entering stationary phase, which in turn would result in higher cell numbers present in the biofilm and reduced resistance to in vitro stress. The mutant was attenuated in the J774A macrophage cell line and was shown to be attenuated in the mouse model of tularaemia, but was able to induce a protective immune response. Therefore, (p)ppGpp appears to be an important intracellular signal, integral to the pathogenesis of F. novicida.

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Section: Discussionmentioning

confidence: 99%

RelA regulates virulence and intracellular survival of Francisella novicida

et al. 2009

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“…The induction of transition-state and early-stationary-phase genes suggests that sorbic acidstressed cells respond as if they experience nutrient limitation. In amino acid-, glucose-, or oxygen-limited cells, the (RelAmediated) stringent response helps to prevent the waste of scarce nutrients (9,26). Hierarchical clustering revealed that only 8 out of 55 (P ϭ 0.017) RelA-dependent positive stringent control genes were significantly induced and that 4 out of 86 (P ϭ 0.79) RelA-dependent negative stringent control genes were significantly repressed.…”

Section: Vol 190 2008 B Subtilis Sorbic Acid Stress Response 1755mentioning

confidence: 99%

Transcriptome Analysis of Sorbic Acid-Stressed Bacillus subtilis Reveals a Nutrient Limitation Response and Indicates Plasma Membrane Remodeling

et al. 2008

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The weak organic acid sorbic acid is a commonly used food preservative, as it inhibits the growth of bacteria, yeasts, and molds. We have used genome-wide transcriptional profiling of Bacillus subtilis cells during mild sorbic acid stress to reveal the growth-inhibitory activity of this preservative and to identify potential resistance mechanisms. Our analysis demonstrated that sorbic acid-stressed cells induce responses normally seen upon nutrient limitation. This is indicated by the strong derepression of the CcpA, CodY, and Fur regulon and the induction of tricarboxylic acid cycle genes, SigL-and SigH-mediated genes, and the stringent response. Intriguingly, these conditions did not lead to the activation of sporulation, competence, or the general stress response. The fatty acid biosynthesis (fab) genes and BkdR-regulated genes are upregulated, which may indicate plasma membrane remodeling. This was further supported by the reduced sensitivity toward the fab inhibitor cerulenin upon sorbic acid stress. We are the first to present a comprehensive analysis of the transcriptional response of B. subtilis to sorbic acid stress.

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“…This so-called 'stringent response' is one of the most important adaptations by which bacteria survive harsh conditions (Braeken et al, 2006;Cashel et al, 1996). The stringent response was originally characterized as the rapid downregulation of stable RNA synthesis during amino acid starvation in Escherichia coli.…”

Section: Introductionmentioning

confidence: 99%

“…Two proteins, RelA and SpoT, are involved in stress-induced ppGpp accumulation in E. coli. RelA induces ppGpp synthesis from GTP or GDP in response to amino acid starvation by interacting with 70S ribosomes, which are activated by the binding of uncharged tRNA to the A site (Braeken et al, 2006;Cashel et al, 1996;Chatterji & Ojha, 2001;Magnusson et al, 2005;Potrykus & Cashel, 2008). SpoT is a bifunctional ppGpp synthetase and hydrolase enzyme.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, many other bacterial species contain only one RelA-SpoT homologue, with both ppGpp synthetase and hydrolase activities, which is therefore often designated RSH (RelA-SpoT homologue). The intracellular ppGpp level is modulated by such bifunctional enzymes through the two distinct active sites (Braeken et al, 2006;Cashel et al, 1996;Hogg et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Heterologous expression of a plant RelA-SpoT homologue results in increased stress tolerance in Saccharomyces cerevisiae by accumulation of the bacterial alarmone ppGpp

et al. 2012

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The bacterial alarmone ppGpp is present only in bacteria and the chloroplasts of plants, but not in mammalian cells or eukaryotic micro-organisms such as yeasts and fungi. The importance of the ppGpp signalling system in eukaryotes has therefore been largely overlooked. Here, we demonstrated that heterologous expression of a relA-spoT homologue (Sj-RSH) isolated from the halophilic plant Suaeda japonica in the yeast Saccharomyces cerevisiae results in accumulation of ppGpp, accompanied by enhancement of tolerance against various stress stimuli, such as osmotic stress, ethanol, hydrogen peroxide, high temperature and freezing. Unlike bacterial ppGpp accumulation, ppGpp was accumulated in the early growth phase but not in the late growth phase. Moreover, nutritional downshift resulted in a decrease in ppGpp level, suggesting that the observed Sj-RSH activity to synthesize ppGpp is not starvation-dependent, contrary to our expectations based on bacteria. Accumulated ppGpp was found to be present solely in the cytosolic fraction and not in the mitochondrial fraction, perhaps reflecting the ribosomeindependent ppGpp synthesis in S. cerevisiae cells. Unlike bacterial inosine monophosphate (IMP) dehydrogenases, the IMP dehydrogenase of S. cerevisiae was insensitive to ppGpp. Microarray analysis showed that ppGpp accumulation gave rise to marked changes in gene expression, with both upregulation and downregulation, including changes in mitochondrial gene expression. The most prominent upregulation (38-fold) was detected in the hypothetical gene YBR072C-A of unknown function, followed by many other known stress-responsive genes. S. cerevisiae may provide new opportunities to uncover and analyse the ppGpp signalling system in eukaryotic cells.

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New horizons for (p)ppGpp in bacterial and plant physiology

Cited by 203 publications

References 68 publications

RelA regulates virulence and intracellular survival of Francisella novicida

RelA regulates virulence and intracellular survival of Francisella novicida

Transcriptome Analysis of Sorbic Acid-Stressed Bacillus subtilis Reveals a Nutrient Limitation Response and Indicates Plasma Membrane Remodeling

Heterologous expression of a plant RelA-SpoT homologue results in increased stress tolerance in Saccharomyces cerevisiae by accumulation of the bacterial alarmone ppGpp

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