Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

1 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

New insights into the regulatory role of the type II antitoxin HigA in Pseudomonas aeruginosa virulence

ABSTRACT: Bacterial type II toxin-antitoxin (TA) systems are abundant genetic elements and involved in a diverse array of physiological processes. They encode a protein antitoxin protein that directly binds and effectively neutralizes the protein toxin. Latest studies have highlighted key roles of the type II TA modules in bacterial virulence and pathogenesis but the underlying mechanisms remains elusive. In this study, we investigated the repression function of antitoxin HigA in Pseudomonas aeruginosa infection. Proteomic analysis of the higA deletion strain revealed enhanced expression levels of proteins contributing to pathogenicity. We further verified that HigA negatively controlled T3SS and T6SS expression by directly interacting with the promoter regions of the respective regulators amrZ and exsA. In that sense, relief of HigA-mediated transcriptional inhibition upon stress stimulation could induce virulence genes. These findings reinforce the crucial roles of type II antitoxin in bacterial infection, which highlights the potential of HigBATA system as a target for antibacterial treatment.

ORGANISM(S): Pseudomonas Aeruginosa Pa14

SUBMITTER: Yongxing He

PROVIDER: PXD026084 | iProX | Fri May 14 00:00:00 BST 2021

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Similar Datasets

The novel type II toxin-antitoxin PacTA modulates Pseudomonas aeruginosa iron homeostasis by obstructing the DNA-binding activity of Fur

Project description:Type II Toxin-antitoxin (TA) systems are widely distributed in bacterial and archaeal genomes with diverse critical cellular functions such as defense against phages, biofilm formation, persistence and virulence. GCN5-related N -acetyltransferase (GNAT) toxin, with an acetyltransferase activity-dependent mechanism of translation inhibition, represents a relatively new and expanding family of type II TA toxins. Here, we describe a group of GNAT-Xre TA modules that are widely distributed among Pseudomonas species and even certain Gram-positive bacteria. We investigate one of its members PacTA (encoded by PA3270/PA3269) from Pseudomonas aeruginosa, and demonstrate that the toxin PacT positively regulates the iron acquisition in P. aeruginosa. Notably, other than arresting translation via acetylating aminoacyl-tRNAs, PacT could directly bind to Fur, a key ferric uptake regulator, to attenuate its DNA-binding affinity and thus permit expression of downstream iron-acquisition-related genes. We further show that expression of the pacTA locus is up-regulated in response to iron starvation and the absence of PacT causes biofilm formation defect and attenuated pathogenesis. Overall, these findings reveal a novel regulation mechanism of GNAT toxin that controls genes involved in iron uptake process and contributes to the bacterial virulence.

2022-05-05 | PXD033699 | iProX

Staphylococcus aureus toxin-antitoxin system

Project description:Type I toxin-antitoxin (TA) systems are widespread genetic modules in bacterial genomes. They express toxic peptides whose overexpression leads to growth arrest or cell death, whereas antitoxins regulate the expression of toxins, acting as labile antisense RNAs. The Staphylococcus aureus (S. aureus) genome contains and expresses several functional type I TA systems, but their biological functions remain unclear. Here we addressed and challenged experimentally, by proteomics, if a type I TA system, the SprF1/SprG1 pair, influences the overall gene expression in S. aureus. Deleted and complemented S. aureus strains were analyzed for their proteomes, both intracellular and extracellular, during growth. Comparison of intracellular proteomes between the strains points on SprF1 antitoxin as an agent downregulating protein expression. In the strain naturally expressing the SprG1 toxin, cytoplasmic proteins are excreted into the medium, but this is not due to unspecific cell leakages. Such toxin-driven release of the cytoplasmic proteins may modulate the host inflammatory response that, in turn, may amplify the S. aureus infection spread.

2021-07-05 | PXD023449 | Pride

Mechanism of translation inhibition by type II GNAT toxins: AtaT, TacT, and ItaT

Project description:Type II toxin-antitoxin (TA) systems are two-gene modules widely distributed among prokaryotes. GNAT toxins associated with the DUF1778 antitoxins represent a large family of type II TAs. GNAT toxins inhibit cell growth by disrupting translation via acetylation of aminoacyl-tRNAs. Using ribosome profiling, we investigated the in vivo substrate specificity of three GNAT toxins: AtaT2, TacT3, and ItaT.

2020-06-17 | GSE148424 | GEO

Expression profile for higA mutant of Pseudomonas aeruginosa PA14

Project description:The previously uncharacterized proteins HigB (unannotated) and HigA (PA4674) of Pseudomonas aeruginosa PA14 were found to form a type II TA system in which antitoxin HigA masks the RNase activity of toxin HigB through direct binding. To determine the physiological role of HigB/HigA in P. aeruginosa, a whole-transcriptome experiment was performed for the higA antitoxin deletion mutant of the PA14 strain compared to the wild-type PA14 strain. The rationale was that for the strain that lacks the antitoxin, the effect of the toxin could be discerned due to enhanced activity of the toxin. Furthermore, toxin HigB reduces production of the virulence factors pyochelin, pyocyanin, swarming, and biofilm formation.

2016-11-04 | GSE74730 | GEO

Expression profile for overproduction of ArT

Project description:Toxin-antitoxin (TA) systems are ubiquitous throughout bacterial and archaeal genomes. TA systems consist of a stable toxin that inhibits growth and a labile antitoxin that prevents toxicity of the toxin. Here we made an artificial TA system (arT/arA) and performed a DNA microarray study for overproduction of the toxin.

2014-05-13 | GSE54271 | GEO

A phage-encoded RNA-binding protein inhibits the antiviral activity of a toxin-antitoxin system

Project description:Bacteria harbor diverse mechanisms to defend themselves against their viral predators, bacteriophages. In response, phages can evolve counter-defense systems, most of which remain poorly understood. In T4-like phages, the gene tifA prevents bacterial defense by the type III toxin-antitoxin (TA) system toxIN, but the mechanism by which TifA inhibits toxIN remains unclear. Here, we show that TifA directly binds both the endoribonuclease ToxN and RNA, leading to the formation of a high molecular weight ribonucleoprotein complex in which ToxN is inhibited. The RNA binding activity of TifA is necessary for its interaction with and inhibition of ToxN. Thus, we propose that TifA inhibits ToxN during phage infection by trapping ToxN on cellular RNA, particularly the abundant 16S rRNA, preventing cleavage of phage transcripts. Taken together, our results reveal a novel mechanism underlying inhibition of a phage-defensive RNase toxin by a small, phage-encoded protein.

2023-12-04 | GSE234211 | GEO

Expression profile for overproduction of ArT

2014-05-13 | E-GEOD-54271 | biostudies-arrayexpress

In planta bacterial multi-omics illuminates regulatory principles underlying plant-pathogen interactions

Project description:Gene regulation of bacterial pathogens in the host is not comprehensively understood due to the difficulty in analyzing genome-wide mRNA and protein expression of bacteria during infection. Here, we jointly analyzed transcriptome and proteome of a foliar bacterial pathogen in plants. Bacterial transcriptome changes can explain to a large extent their proteome changes in resistant and susceptible plants. However, a part of bacterial type III secretion system was suppressed by plant immunity preferentially at the protein level. Also, gene co-expression analysis uncovered previously unknown gene regulatory modules underlying bacterial virulence. Collectively, integrated in planta bacterial omics provides molecular insights into multiple layers of bacterial gene regulation that contributes to virulence and roles of plant immunity in controlling it.

2020-04-30 | PXD015839 | Pride

High-throughput suppressor selection of a type I toxin-antitoxin system in Helicobacter pylori

Project description:As the number of bacterial genomes and transcriptomes increases, so does the number of newly identified toxin–antitoxin (TA) systems. However, their functional characterization remains challenging, often requiring the use of overexpression vectors that can lead to misinterpretations. To fill this gap, we developed a systematic approach called FASTBAC-Seq (Functional AnalysiS of Toxin–Antitoxin Systems in BACteria by Deep Sequencing). Combining life/death phenotypic selection with next-generation sequencing, FASTBAC-Seq allows the rapid identification of loss-of- function (toxicity) mutations in toxin-encoding genes belonging to TA loci with nucleotide resolution. Here, we apply this new tool to study aapA3/IsoA3, a member of a new family of type I TA systems hosted on the chromosome of the major human gastric pathogen Helicobacter pylori.

2019-08-30 | GSE121423 | GEO

VapCs of Mycobacterium tuberculosis Cleave RNAs Essential for Translation

Project description:The major human pathogen Mycobacterium tuberculosis can survive in the host organism for decades without causing symptoms. A large cohort of Toxin-Antitoxin (TA) modules contribute to this persistence. Of these, 48 TA modules belong to the vapBC (virulence associated protein) gene family. VapC toxins are PIN domain endonucleases that, in Enterobacteria, inhibit translation by site-specific cleavage of initiator tRNA. In contrast, VapC20 of M. tuberculosis inhibits translation by site-specific cleavage of the universally conserved Sarcin-Ricin loop (SRL) in 23S rRNA. Here we identify cleavage targets for 12 VapCs from M. tuberculosis by applying UV-crosslinking and deep sequencing. Remarkably, these VapCs are all endoribo-nucleases that cleave RNA targets that are essential for decoding at the ribosomal A-site. Eleven VapCs cleave specific tRNAs while one exhibits SRL cleavage activity. These findings suggest that multiple vapBC modules contribute to the survival of M. tuberculosis in its human host by reducing the level of translation.

2017-08-14 | GSE85905 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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