Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HipBA toxin-antitoxin system Caulobacter crescentus.

ABSTRACT: Antibiotic persistence is a transient phenotypic state during which a bacterium can withstand otherwise lethal antibiotic exposure or environmental stresses. In Escherichia coli, persistence is promoted by the HipBA toxin-antitoxin system. The HipA toxin functions as a serine/threonine kinase that inhibits cell growth, while the HipB antitoxin neutralizes the toxin. E. coli HipA inactivates the glutamyl-tRNA synthetase GltX, which inhibits translation and triggers the highly conserved stringent response. Although hipBA operons are widespread in bacterial genomes, it is unknown if this mechanism is conserved in other species. Here we describe the functions of three hipBA modules in the alpha-proteobacterium Caulobacter crescentus. The HipA toxins have different effects on growth and macromolecular syntheses, and they phosphorylate distinct substrates. HipA1 and HipA2 contribute to antibiotic persistence during stationary phase by phosphorylating the aminoacyl-tRNA synthetases GltX and TrpS. The stringent response regulator SpoT is required for HipA-mediated antibiotic persistence, but persister cells can form in the absence of all hipBA operons or spoT, indicating that multiple pathways lead to persister cell formation in C. crescentus.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Caulobacter Crescentus (strain Na1000 / Cb15n)

SUBMITTER: Celine Henry

LAB HEAD: Celine Henry

PROVIDER: PXD015525 | Pride | 2020-02-06

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	Caulo_01_IMAC.raw	Raw
	Caulo_01_IMAC.xml	Xml
	Caulo_01_TiO2.raw	Raw
	Caulo_01_TiO2.xml	Xml
	Caulo_02_IMAC.raw	Raw

Items per page:

1 - 5 of 44

Similar Datasets

Serine-Threonine Kinase Encoded by a Split hipA Homologous Gene of Escherichia coli Inhibits Tryptophanyl-tRNA Synthetase

Project description:Type II toxin – antitoxin modules encode a stable toxin that inhibits translation, replication or cell wall synthesis and an unstable protein antitoxin that neutralizes the toxin by direct protein – protein contact. The hipBA module of Escherichia coli K-12 codes for HipA, a eukaryote-like serine/threonine protein kinase that phosphorylates and inhibits glutamyl-tRNA synthetase. Induction of hipA leads to a reduced level of charged glutamyl tRNA that, in turn, inhibits translation, induces RelA-dependent (p)ppGpp synthesis and multidrug tolerance (persistence). Here, we describe the discovery of a three-component TA module hipBST of E. coli O127:H6 strain E2348/69 that encodes HipT, which exhibits sequence similarity with the C-terminal part of HipA. We show that HipT is a kinase that phosphorylates tryptophanyl-tRNA synthetase in vitro at conserved serine residue. Consistently, induction of hipT inhibits cell growth, stimulates production of stringent factor (p)ppGpp and induces persistence. Remarkably, the gene immediately upstream of hipT, called hipS, encodes a small protein that exhibits sequence similarity with the C-terminal part of HipA. Unexpectedly, HipT kinase is neutralized by HipS in vivo whereas the third component, HipB0127, encoded by the first gene of the operon, does not counteract HipT kinase. However, HipB contains a HTH DNA-binding domain and may function to autoregulate the hipBST operon. Thus, hipA has been split into two genes, hipS and hipT that function as a toxin – antitoxin pair.

2019-06-24 | PXD012023 | Pride

Bacterial single cell RNA-seq unveils cyclic-di-GMP as an antitoxin critical for antibiotic tolerance in biofilm [scRNA-seq]

Project description:Biofilms are heterogeneous bacterial communities featured by high persister prevalence, responsible for antibiotic tolerance. However, the mechanisms underlying persister formation within biofilms remained ambiguous. Here, by developing and utilizing a ribosomal RNA depleted bacterial single-cell RNA-seq method, RiboD-mSPLiT, we resolved biofilm heterogeneity and discovered pdeI as a marker gene for persister subgroup within biofilms. Remarkably, our findings elucidated that PdeI upregulates cellular levels of c-di-GMP, which acts as an antitoxin to modulate the toxicity of toxin protein HipH. HipH localizes on nucleoid and functions as a potent DNase, inducing cells into a viable but non-culturable state. Conversely, c-di-GMP interacts with HipH, reducing its genotoxic effects and enabling cells to enter a persister state, resulting in drug tolerance. Importantly, by targeting this toxin-antitoxin system, we repressed drug tolerance in Uropathogenic Escherichia coli infections, offering promising therapeutic strategies against chronic and relapsing infections.

2024-02-20 | GSE239504 | GEO

Bacterial single cell RNA-seq unveils cyclic-di-GMP as an antitoxin critical for antibiotic tolerance in biofilm [RNA-seq]

2024-02-20 | GSE239503 | GEO

Bacterial single cell RNA-seq unveils cyclic-di-GMP as an antitoxin critical for antibiotic tolerance in biofilm [ChIP-seq]

2024-02-20 | GSE239502 | GEO

A HigB-like toxin induces non-replicating Salmonella inside macrophages by inhibiting RNase III-dependent rRNA maturation [sehB_RNA-Seq]

Project description:Many bacteria are often resistant to antibiotic treatment and drugs because, even if these drugs are effective, bacteria can slow down their growth rate and thus attenuate the effectiveness of the drug. A similar growth-rate control is detected in pathogenic bacteria that infect and persist inside their hosts. The bacterial growth rate within host cells can be regulated by multiple signaling pathways, most of which are still unknown. A toxin-antitoxin (TA) system is one of the candidates for controlling bacterial growth because the TA system could slow down growth by expressing a toxin component. The toxin protein can be neutralized by the antitoxin component, serving as a non-heritable phenotypic switch for growth rate. In this study, we investigated a type II toxin-antitoxin system from the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium. We characterized residues required for toxin’s activity and a potential mechanism of the toxin by searching for its target via bacterial two-hybrid screening. Understanding the underlying mechanism of toxin-mediated persister formation and growth rate control within host cells will provide a new alternative to treat antibiotic resistant bacteria or intracellular bacteria surviving within host cells.

2024-06-21 | GSE269990 | GEO

A HigB-like toxin induces non-replicating Salmonella inside macrophages by inhibiting RNase III-dependent rRNA maturation [sehA_RNA-Seq]

2024-06-21 | GSE269989 | GEO

Persistence of BW25113 mqsR producing MqsR 2-1 vs. producing wild-type MqsR with ampicillin

Project description:Persisters are a subpopulation of metabolically-dormant cells in biofilms that are resistant to antibiotics; hence, understanding persister cell formation is important for controlling bacterial infections. Previously we discerned that MqsR and MqsA of Escherichia coli are a toxin/antitoxin pair that influence persister cell production via their regulation of Hha, CspD, and HokA. Here, to gain more insights into the origin of persisters, we used protein engineering to increase the toxicity of toxin MqsR by reasoning it would be easier to understand the effect of this toxin if it were more toxic. We found that two mutations (K3N and N31Y) increase the toxicity four fold and increase persistence 73 fold compared to native MqsR by making the protein less labile. A whole transcriptome study revealed that the MqsR variant represses acid resistance genes (gadABCEWX and hdeABD), multidrug resistance genes (mdtEF), and osmotic resistance genes (osmEY). Corroborating these microarray results, deletion of rpoS as well as the genes that the master stress response regulator RpoS controls, gadB, gadX, mdtF, and osmY, increased persister formation dramatically to the extent that nearly the whole population became persistent. Therefore, the more toxic MqsR increases persistence by decreasing the ability of the cell to respond to antibiotic stress through its RpoS-based regulation of acid resistance, multidrug resistance, and osmotic resistance systems.

2012-04-03 | GSE31054 | GEO

E. coli BW25113 K-12 hfq vs. wild-type persister

Project description:Persisters are cells which evade stresses like antibiotics and which are characterized by reduced metabolism and a lack of genetic alterations required to achieve this state. We showed previously that MqsR and MqsA of Escherichia coli are a toxin-antitoxin pair that influence cell physiology (e.g., biofilm formation and motility) via RNase activity as well as through regulation of toxin CspD. Here, we show that deletion of the mqsRA locus decreases persister cell formation and, consistent with this result, overexpression of MqsR increases persister cell formation. Furthermore, toxins Hha, CspD, and HokA increase persister cell formation. In addition, by overproducing MqsR in a series of isogenic mutants, we show that Hha and CspD are necessary for persister cell formation via MqsR overexpression. Surprisingly, Hfq, a small RNA chaperone, decreases persistence. A whole-transcriptome study shows that Hfq induces transport-related genes (oppA, oppB, oppC, oppD, oppF, and dppA), outer membrane protein-related genes (ybfM and ybfN), toxins (hha), and proteases (clpX, clpP, and lon). Taken together, these results indicate that toxins CspD and Hha influence persister cell formation via MqsR and that Hfq plays an important role in the regulation of persister cell formation via regulation of transport or outer membrane proteins. Strains: E. coli BW25113 K-12 hfq deleted mutant vs. wild-type Medium: LB Culture: Planktonic cell grown OD=0.5, adjusted OD=1.0, and then exposed to 100 ug/mL ampicillin for 2 h.

2009-11-07 | E-GEOD-18852 | biostudies-arrayexpress

Expression profile for overproduction of DosP

Project description:Persister cells are a sub-population of all bacterial cultures which exhibit a non-inheritable, multi-drug tolerance when subjected to lethal antibiotic challenge. These persisters arise as a result of metabolic dormancy, and can resume growth subsequent to antibiotic challenge, leading to recalcitrance of bacterial infections. Overproduction of DosP, an oxygen sensing protein with phosphodiesterase activity, increases bacterial persistence. Here we performed a microarray to determine the expression profile induced by DosP as a means to elucidate mechanisms of persister cell formation. dosP was overexpressed in Escherichia coli K-12 BW25113 and compared to the empty vector.

2014-09-15 | E-GEOD-47427 | biostudies-arrayexpress

Proteome dynamics in persisting and resuscitating bacterial cells

Project description:Bacterial persister cells become transiently tolerant to antibiotics by restraining their growth and metabolic activity. Detailed molecular characterization of bacterial persistence is hindered by low count of persisting cells and the need for their isolation. Here we used sustained addition of stable isotope-labeled lysine to selectively label the proteome of hipA-induced persisting and hipB-induced resuscitating E. coli cells in minimal medium after antibiotic treatment. Time-resolved, 24-hour measurement of label incorporation allowed detection of more than 500 newly synthetized proteins in persister cells, demonstrating low but widespread protein synthesis during persistence. Many essential proteins were newly synthesized; several ribosome-associated proteins showed unusually high synthesis levels and are involved in maintenance of persistence. At the onset of resuscitation, cells synthesized ABC transporters, restored translation machinery and resumed metabolism by inducing glycolysis and biosynthesis of amino acids. This dataset provides an unprecedented insight into the processes governing persistence and resuscitation of bacterial cells.

2021-07-30 | PXD018153 | Pride

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