(p)ppGpp – an important player during heat shock response

Driller, Kristina; Cornejo, Fabián A.; Turgay, Kürşad

doi:10.1093/femsml/uqad017

Cited by 3 publications

(1 citation statement)

References 95 publications

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“…Furthermore, groEL (2.4-fold) and groES (4.9-fold), which are part of the CtsR/HrcA regulon, were found to be upregulated, indicative of proteotoxic stress. Both protein complexes were upregulated during proteotoxic stress, which leads to protein misfolding and aggregation 30 . These findings are consistent with the slightly elevated protein aggregates detected in the (p)ppGpp 0 mutant during stationary phase starvation (Fig.…”

Section: Impact Of a Lack Of (P)ppgpp Biosynthesis And Gtp Imbalance ...mentioning

confidence: 99%

(p)ppGpp-mediated GTP homeostasis ensures the survival and antibiotic tolerance ofStaphylococcus aureusduring starvation by preserving the proton motive force

Salzer,

Ingrassia,

Sauer

et al. 2024

Preprint

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Upon nutrient limitation bacteria enter a nongrowing state, which allow bacterial survival and antibiotic tolerance. The mechanisms whether and how the messenger molecule (p)ppGpp contributes to the transition in Firmicutes is debated. Here we show forStaphylococcus aureusthat (p)ppGpp-dependent restriction of the GTP pool is essential for the culturability of starved cells and for antibiotic tolerance. Elevated GTP levels in a starving (p)ppGpp-deficient mutant lead to a division-incompetent, dormant state characterized by reduced metabolic activity and alterations in membrane function and architecture. GTP level control of nucleotide sensitive promoters result in transcriptional downregulation of gene of the TCA cycle and electron transport chain. Increasing transcription ofqoxABCD, a terminal oxidase of the respiratory chain, through mutation of the transcriptional start site partially restored the culturability of the (p)ppGpp-deficient mutant. Furthermore, we showed that the maintenance of proton motive force under nutritional stress contributes to antibiotic tolerance, supporting the idea of applying (p)ppGpp or PMF inhibitors to combat antibiotic-tolerant bacteria.

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Section: Impact Of a Lack Of (P)ppgpp Biosynthesis And Gtp Imbalance ...mentioning

confidence: 99%

(p)ppGpp-mediated GTP homeostasis ensures the survival and antibiotic tolerance ofStaphylococcus aureusduring starvation by preserving the proton motive force

Salzer,

Ingrassia,

Sauer

et al. 2024

Preprint

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Structural and Evolutionary Analysis of Proteins Endowed with a Nucleotidyltransferase, or Non-canonical Palm, Catalytic Domain

Jácome

2024

J Mol Evol

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Many polymerases and other proteins are endowed with a catalytic domain belonging to the nucleotidyltransferase fold, which has also been deemed the non-canonical palm domain, in which three conserved acidic residues coordinate two divalent metal ions. Tertiary structure-based evolutionary analyses provide valuable information when the phylogenetic signal contained in the primary structure is blurry or has been lost, as is the case with these proteins. Pairwise structural comparisons of proteins with a nucleotidyltransferase fold were performed in the PDBefold web server: the RMSD, the number of superimposed residues, and the Qscore were obtained. The structural alignment score (RMSD × 100/number of superimposed residues) and the 1-Qscore were calculated, and distance matrices were constructed, from which a dendogram and a phylogenetic network were drawn for each score. The dendograms and the phylogenetic networks display well-defined clades, reflecting high levels of structural conservation within each clade, not mirrored by primary sequence. The conserved structural core between all these proteins consists of the catalytic nucleotidyltransferase fold, which is surrounded by different functional domains. Hence, many of the clades include proteins that bind different substrates or partake in non-related functions. Enzymes endowed with a nucleotidyltransferase fold are present in all domains of life, and participate in essential cellular and viral functions, which suggests that this domain is very ancient. Despite the loss of evolutionary traces in their primary structure, tertiary structure-based analyses allow us to delve into the evolution and functional diversification of the NT fold.

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The stringent response is strongly activated in the antibiotic producing strain, Streptomyces coelicolor

Lejeune,

Cornu,

Sago

et al. 2024

Research in Microbiology

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(p)ppGpp – an important player during heat shock response

Cited by 3 publications

References 95 publications

(p)ppGpp-mediated GTP homeostasis ensures the survival and antibiotic tolerance ofStaphylococcus aureusduring starvation by preserving the proton motive force

(p)ppGpp-mediated GTP homeostasis ensures the survival and antibiotic tolerance ofStaphylococcus aureusduring starvation by preserving the proton motive force

Structural and Evolutionary Analysis of Proteins Endowed with a Nucleotidyltransferase, or Non-canonical Palm, Catalytic Domain

The stringent response is strongly activated in the antibiotic producing strain, Streptomyces coelicolor

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