Browse
Submit Data
Databases
API
Help

Dataset Information

6 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The extended (p)ppGpp family: New dimensions in Stress response.

ABSTRACT: Second messenger (p)ppGpp mediated stress response plays a crucial role in bacterial persistence and multiple drug resistance. In E. coli, (p)ppGpp binds to RNA polymerase and upregulates the transcription of genes essential for stress response while concurrently downregulating the expression of genes critical for growth and metabolism. Recently, the family of alarmone molecules has expanded to pppGpp, ppGpp, pGpp & (pp)pApp as distinct members. These molecules may help in fine-tuning stress responses in different hostile conditions. Do all of these molecules bind to RNA polymerase? Do they compete with each other or complement each other's functions is still not clear. Earlier, others and we have synthesized artificial analogs of (p)ppGpp that inhibited (p)ppGpp synthesis and long-term survival in M. smegmatis and in B. subtilis suggesting that analogs could compete with each other. Understanding the interplay of these molecules will allow deciphering novel pathways that can be potentially subjected to the therapeutic intervention. In this article, we have reviewed newly characterized second messengers and discussed their mode of action. We have also documented the progress made to-date in understanding the molecular basis of regulation of transcription by second messenger ppGpp, pppGpp, and pGpp.

SUBMITTER: Syal K

PROVIDER: S-EPMC8610335 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Stress response regulators identified through genome-wide transcriptome analysis of the (p)ppGpp-dependent response in Rhizobium etli.

Project description:BACKGROUND: The alarmone (p)ppGpp mediates a global reprogramming of gene expression upon nutrient limitation and other stresses to cope with these unfavorable conditions. Synthesis of (p)ppGpp is, in most bacteria, controlled by RelA/SpoT (Rsh) proteins. The role of (p)ppGpp has been characterized primarily in Escherichia coli and several Gram-positive bacteria. Here, we report the first in-depth analysis of the (p)ppGpp-regulon in an ?-proteobacterium using a high-resolution tiling array to better understand the pleiotropic stress phenotype of a relA/rsh mutant. RESULTS: We compared gene expression of the Rhizobium etli wild type and rsh (previously rel) mutant during exponential and stationary phase, identifying numerous (p)ppGpp targets, including small non-coding RNAs. The majority of the 834 (p)ppGpp-dependent genes were detected during stationary phase. Unexpectedly, 223 genes were expressed (p)ppGpp-dependently during early exponential phase, indicating the hitherto unrecognized importance of (p)ppGpp during active growth. Furthermore, we identified two (p)ppGpp-dependent key regulators for survival during heat and oxidative stress and one regulator putatively involved in metabolic adaptation, namely extracytoplasmic function sigma factor EcfG2/PF00052, transcription factor CH00371, and serine protein kinase PrkA. CONCLUSIONS: The regulatory role of (p)ppGpp in R. etli stress adaptation is far-reaching in redirecting gene expression during all growth phases. Genome-wide transcriptome analysis of a strain deficient in a global regulator, and exhibiting a pleiotropic phenotype, enables the identification of more specific regulators that control genes associated with a subset of stress phenotypes. This work is an important step toward a full understanding of the regulatory network underlying stress responses in ?-proteobacteria.

| S-EPMC3188799 | biostudies-literature

A New Extended-X Family of Distributions: Properties and Applications.

Project description:During the past couple of years, statistical distributions have been widely used in applied areas such as reliability engineering, medical, and financial sciences. In this context, we come across a diverse range of statistical distributions for modeling heavy tailed data sets. Well-known distributions are log-normal, log-t, various versions of Pareto, log-logistic, Weibull, gamma, exponential, Rayleigh and its variants, and generalized beta of the second kind distributions, among others. In this paper, we try to supplement the distribution theory literature by incorporating a new model, called a new extended Weibull distribution. The proposed distribution is very flexible and exhibits desirable properties. Maximum likelihood estimators of the model parameters are obtained, and a Monte Carlo simulation study is conducted to assess the behavior of these estimators. Finally, we provide a comparative study of the newly proposed and some other existing methods via analyzing three real data sets from different disciplines such as reliability engineering, medical, and financial sciences. It has been observed that the proposed method outclasses well-known distributions on the basis of model selection criteria.

| S-EPMC7270997 | biostudies-literature

(p)ppGpp-mediated stress response induced by defects in outer membrane biogenesis and ATP production promotes survival in Escherichia coli.

Project description:Cellular growth requires a high level of coordination to ensure that all processes run in concert. The role of the nucleotide alarmone (p)ppGpp has been extensively studied in response to external stresses, such as amino acid starvation, in Escherichia coli, but much less is known about the involvement of (p)ppGpp in response to perturbations in intracellular processes. We therefore employed CRISPRi to transcriptionally repress essential genes involved in 14 vital processes and investigated whether a (p)ppGpp-mediated response would be induced. We show that (p)ppGpp is produced and required for a pertinent stress response during interference with outer membrane biogenesis and ADP synthesis specifically. When these processes were perturbed via the transcriptional repression of essential genes, wild type E. coli MG1655 ceased growing and entered a semi-dormant state, whereas isogenic (p)ppGpp0 cells continued to grow uncontrollably to the point of lysis. Furthermore, in vivo measurements revealed that the ATP levels were intrinsically offset in (p)ppGpp0 cells, further indicating a role for the alarmone in cellular energy homeostasis. In summary, our investigation suggests that (p)ppGpp acts as a coordinator of cell growth in response to imbalances in outer membrane biogenesis and adenosine ribonucleotide synthesis, elucidating novel roles for (p)ppGpp in bacterial physiology.

| S-EPMC6393671 | biostudies-other

BrevicidineB, a New Member of the Brevicidine Family, Displays an Extended Target Specificity.

Project description:The group of bacterial non-ribosomally produced peptides (NRPs) has formed a rich source for drug development. Brevicidine, a bacterial non-ribosomally produced cyclic lipo-dodecapeptide, displays selective antimicrobial activity against Gram-negative pathogens. Here, we show that brevicidineB, which contains a single substitution (Tyr2 to Phe2) in the amino acid sequence of the linear part of brevicidine, has a broadened antimicrobial spectrum, showing bactericidal activity against both Gram-negative (with a MIC value of 2 to 4 mg/L) and Gram-positive (with a MIC value of 2 to 8 mg/L) pathogens. Compared with an earlier reported member of the brevicidine family, the broadened antimicrobial spectrum of brevicidineB is caused by its increased membrane disruptive capacity on Gram-positive pathogens, which was evidenced by fluorescence microscopy assays. In addition, DiSC3(5) and resazurin assays show that brevicidine and brevicidineB exert their antimicrobial activity against Gram-negative bacteria via disrupting the proton motive force of cells. Notably, as a brevicidine family member, brevicidineB also showed neither hemolytic activity nor cytotoxicity at a high concentration of 64 mg/L. This study provides a promising antibiotic candidate (brevicidineB) with a broad antimicrobial spectrum, and provides novel insights into the antimicrobial mode of action of brevicidines.

| S-EPMC8219939 | biostudies-literature

Coping with COVID Stress: Maladaptive and Adaptive Response Styles Predicting College Student Internalizing Symptom Dimensions.

Project description:The COVID-19 pandemic significantly disrupted daily life for undergraduates and introduced new stressors (e.g., campus closures). How individuals respond to stressors can interact with stress to increase disorder risk in both unique and transdiagnostic ways. The current study examined how maladaptive and adaptive stress response styles moderated the perceived severity of COVID-related stressors effect on general and specific internalizing dimensions at the beginning of the COVID-19 pandemic in a combined undergraduate sample across two universities (N = 451) using latent bifactor modeling and LASSO modeling to identify optimal predictors. Results showed that perceived stress severity and maladaptive response styles (not adaptive response styles or interactions between stress and response styles) were associated with both common and specific internalizing dimensions. Results suggest additive associations of stress severity and maladaptive coping with internalizing symptoms during the pandemic's beginning, and provide important insights for screening, prevention, and intervention during future public health crises.Supplementary informationThe online version contains supplementary material available at 10.1007/s10862-022-09975-7.

| S-EPMC9305060 | biostudies-literature

Stress response regulators identified through genome-wide transcriptome analysis of the (p)ppGpp-dependent response in Rhizobium etli

Project description:The impact on gene expression by the alarmone (p)ppGpp during growth and non-growth was determined by comparing the transcriptome of R. etli CFN42 wild type and rel mutant. This allowed us to better understand the pleiotropic stress phenotype of the rel mutant as well as identifying specific (p)ppGpp-dependent stress regulators.

2010-09-15 | GSE23961 | GEO

Synthetic (p)ppGpp Analogue Is an Inhibitor of Stringent Response in Mycobacteria.

Project description:Bacteria elicit an adaptive response against hostile conditions such as starvation and other kinds of stresses. Their ability to survive such conditions depends, in part, on stringent response pathways. (p)ppGpp, considered to be the master regulator of the stringent response, is a novel target for inhibiting the survival of bacteria. In mycobacteria, the (p)ppGpp synthetase activity of bifunctional Rel is critical for stress response and persistence inside a host. Our aim was to design an inhibitor of (p)ppGpp synthesis, monitor its efficiency using enzyme kinetics, and assess its phenotypic effects in mycobacteria. As such, new sets of inhibitors targeting (p)ppGpp synthesis were synthesized and characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. We observed significant inhibition of (p)ppGpp synthesis by RelMsm in the presence of designed inhibitors in a dose-dependent manner, which we further confirmed by monitoring the enzyme kinetics. The Rel enzyme inhibitor binding kinetics were investigated by isothermal titration calorimetry. Subsequently, the effects of the compounds on long-term persistence, biofilm formation, and biofilm disruption were assayed in Mycobacterium smegmatis, where inhibition in each case was observed. In vivo, (p)ppGpp levels were found to be downregulated in M. smegmatis treated with the synthetic inhibitors. The compounds reported here also inhibited biofilm formation by the pathogen Mycobacterium tuberculosis The compounds were tested for toxicity by using an MTT assay with H460 cells and a hemolysis assay with human red blood cells, for which they were found to be nontoxic. The permeability of compounds across the cell membrane of human lung epithelial cells was also confirmed by mass spectrometry.

| S-EPMC5444170 | biostudies-other

Functional genomics reveals extended roles of the Mycobacterium tuberculosis stress response factor sigmaH.

Project description:Mycobacterium tuberculosis is one of the most successful pathogens of humankind. During infection, M. tuberculosis must cope with and survive against a variety of different environmental conditions. Sigma factors likely facilitate the modulation of the pathogen's gene expression in response to changes in its extracellular milieu during infection. sigma(H), an alternate sigma factor encoded by the M. tuberculosis genome, is induced by thiol-oxidative stress, heat shock, and phagocytosis. In response to these conditions, sigma(H) induces the expression of sigma(B), sigma(E), and the thioredoxin regulon. In order to more effectively characterize the transcriptome controlled by sigma(H), we studied the long-term effects of the induction of sigma(H) on global transcription in M. tuberculosis. The M. tuberculosis isogenic mutant of sigma(H) (Delta-sigma(H)) is more susceptible to diamide stress than wild-type M. tuberculosis. To study the long-term effects of sigma(H) induction, we exposed both strains to diamide, rapidly washed it away, and resumed culturing in diamide-free medium (post-diamide stress culturing). Analysis of the effects of sigma(H) induction in this experiment revealed a massive temporal programming of the M. tuberculosis transcriptome. Immediately after the induction of sigma(H), genes belonging to the functional categories "virulence/detoxification" and "regulatory proteins" were induced in large numbers. Fewer genes belonging to the "lipid metabolism" category were induced, while a larger number of genes belonging to this category were downregulated. sigma(H) caused the induction of the ATP-dependent clp proteolysis regulon, likely mediated by a transcription factor encoded by Rv2745c, several members of the mce1 virulence regulon, and the sulfate acquisition/transport network.

| S-EPMC2698404 | biostudies-literature

Role of Arabidopsis NHL family in ABA and stress response.

Project description:Based on their sequence homology to Arabidopsis NDR1 and tobacco (Nicotiana tabacum) HIN1, 45 NHL (NDR1/HIN1-like) family genes are found in Arabidopsis genome. Recently, we reported that overexpression of NHL6, a member of NHL family, modulated seed germination under abiotic stresses through affecting ABA biosynthesis and signaling. We also carried out qPCR and investigated the expression of the other 8 member genes (NHL7a, 16, 17, 21, 25, 26, 41, 43) whose transcriptional data are publicly unavailable, and found that expression of NHL17 was induced more than 2 folds in ABA treated seedlings. Furthermore, in addition to the plasma membrane localization, YFP-NHL6 fusion protein was also observed in the cytosol (as dots) or on the membrane of small vacuoles or vesicles. As a member of the pathogen infection related genes, expression of NHL6 was significantly induced by salicylic acid and NHL6s are evolutionarily conserved among different plant species. A working model of NHL6 in ABA response was proposed.

| S-EPMC4977461 | biostudies-other

Functional Genomics Reveals Extended Roles of the Mycobacterium tuberculosis Stress Response Factor sigmaH

Project description:DNA Microarray based comparison of M. tuberculosis and its isogenic delta-sigmaH mutant for an extended period of time, using a diamide-stress and removal strategy (post-diamide stress or PDS) Raw data has been requested of, but not provided by, the submitter.

2009-09-04 | GSE15608 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data