Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-sequencing analysis examining how the Vibrio cholerae MARTX toxin and its inidividual effector domains modulate the transcriptome of human intestinal epithelial cells.

ABSTRACT: MARTX toxins are large single polypeptide bacterial toxins that translocate multiple cytotoxic and functionally independent effector domains into the cytosol of a target eukaryotic cell. Pandemic Vibrio cholerae El Tor O1 strains secrete a MARTX toxin with three effector domains — the actin crosslinking domain (ACD), the Rho inactivation domain (RID), and the alpha/beta-hydrolase domain (ABH) — to regulate innate immunity and enhance colonization. The goal of this study was to compare changes in the transcriptome of human intestinal epithelial cells (IECs) treated with V. cholerae modified to secret a toxin with only one effector domain to the transcriptome of cells treated with V. cholerae secreting the wild type MARTX toxin that delivers all three effector domains simultaneously. We demonstrate that when all three effectors are delivered there is no change in transcriptional response of IECs compared to untreated cells. However, when only ACD is delivered, transcriptional profiling revealed a significant proinflammatory response is activated. These data suggests that V. cholerae may utilize co-delivery of RID and/or ABH to silence the intestinal immune response to ACD activity. These data provide insight into how the V. cholerae MARTX toxin effector domains function together to alter the innate immune response of IECs during bacterial infection.

ORGANISM(S): Homo sapiens

PROVIDER: GSE125453 | GEO | 2019/01/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Vibrio vulnificus MARTX toxin effector domains differentially remodel the transcriptional response of intestinal epithelial cells

Project description:Vibrio vulnificus is an foodborne pathogen that can cause gastroenteritis and septicemia in humans. V. vulnificus secretes a multifunctional autoprocessing repeats-in-toxin (MARTX) toxin as an essential virulence factor to cause disease. MARTX toxins are pore-forming toxins that translocate multiple functionally independent effector domains into a target cell. MARTX toxins of V. vulnificus can contain anywhere from 3 to 5 of the 10 identified effector domains and strains with different effector repertories having varying virulence potential. The goal of this study was to compare how different effector combinations from an F-type MARTX toxin differentially remodel the transcriptional response of human intestinal epithelial cells (IECs). F-type MARTX toxins contain five effector domains – the actin crosslinking domain (ACD), two copies the makes caterpillar floppy-like domain (MCF), and alpha-beta hydrolase (ABH) domain, and the Ras/Rap1 specific endopeptidase (RRSP). Cultured human IECs were treated with V. vulnificus or strains modified to secrete a toxin with only ACD, ACD with MCF-ABH, ACD with RRSP, or no active effectors. We demonstrate that when no active effectors are present, the bacterium induces minimal changes in the transcriptional profile of IECs. However, the strains containing different effector combinations each uniquely remodeled the transcriptional profile of IECs. These data provide insight into how V. vulnificus strains with varying effector combinations can differentially regulate the host cell response to cause disease.

2021-11-21 | GSE189194 | GEO

Invasion strategy of pathogenic bacteria is reinforced by a MARTX toxin effector duet

Project description:Multiple bacterial genera take advantage of the multifunctional utoprocessing repeats-in-toxin (MARTX) toxin to invade host cells1. Secretion of the MARTX toxin by Vibrio vulnificus, a deadly opportunistic pathogen that causes primary septicemia, the precursor of sepsis2-5, is a major driver of infection6,7; however, it is not clear how the toxin induces septicemia. Here, we report the crystal and cryo-electron microscopy (EM) structures of a toxin effector duet comprising the domain of unknown function in the first position (DUF1)/Rho inactivation domain (RID) complexed with human targets. These structures reveal how the duet is used by bacteria as a potent weapon. The data show that DUF1 acts as a RID-dependent transforming NADase domain (RDTND) that disrupts NAD+ homeostasis by hijacking calmodulin. The cryo-EM structure of the RDTND-RID duet complexed with calmodulin and Rac1, together with immunological analyses in vitro and in mice, provide mechanistic insight into how V. vulnificus uses the duet to suppress ROS generation by depleting NAD(P)+ and modifying Rac1 in a mutually-reinforcing manner that ultimately paralyzes first line immune responses, promotes dissemination of invaders, and induces sepsis. These data may allow development of tools or strategies to combat MARTX toxin-related human diseases.

2024-07-05 | PXD047927 | Pride

Mounting, structure and autocleavage of a type VI secretion-associated Rhs polymorphic toxin

Project description:Bacteria have evolved effectors or toxins to outcompete other bacteria or to hijack host cell pathways. One broad family of bacterial polymorphic toxins regroups multidomain proteins with a modular organization, that comprise a C-terminal toxin domain fused to a N-terminal domain that adapt to the delivery apparatus. Polymorphic toxins include bacteriocins, contact-dependent growth inhibition systems, and specialized Hcp, VgrG, PAAR or Rhs Type VI secretion (T6SS) components. We recently described and characterized Tre23, a toxin domain fused to a T6SS-associated Rhs protein in Photorhabdus laumondii. Here, we show that the Rhs polymorphic toxin forms a complex with the T6SS spike protein VgrG and a cognate chaperone EagR. Using truncation derivatives and cross-linking mass spectrometry, we demonstrate that VgrG-EagR-Rhs complex formation requires the VgrG C-terminal β-helix and the Rhs Nterminal prePAAR and PAAR domains. We then report the cryo-electron-microscopy structure of the Rhs-EagR complex, demonstrating that the Rhs central region forms a β-barrel cage-like structure that encapsulates the C-terminal toxin domain, and provide evidence for processing of the Rhs protein through aspartyl autoproteolysis. We propose a model for Rhs loading on the T6SS, transport and delivery into the target cell.

2021-11-30 | PXD028652 | Pride

Salmonella antibacterial Rhs polymorphic toxin inhibits translation through ADP-ribosylation of EF-Tu P-loop

Project description:Rearrangement hot spots (Rhs) proteins are members of the broad family of polymorphic toxins. Polymorphic toxins are modular proteins composed of an N-terminal region that specifies their mode of secretion into the medium or into the target cell, a central delivery module and a C-terminal domain that has toxic activity. Here, we structurally and functionally characterize the C-terminal toxic domain of the antibacterial Rhsmain protein, which is delivered by the Type VI secretion system of Salmonella enterica Typhimurium. We show that this domain adopts an ADP-ribosyltransferase fold and inhibits protein synthesis by transferring an ADP-ribose group from NAD+ to the elongation factor EFTu. This modification is specifically placed on the sidechain of the conserved D21 residue located on the P-loop of the EF-Tu G-domain. Finally, we demonstrate that its cognate immunity protein neutralizes Rhsmain C-terminal toxin activity by acting like a lid that closes the catalytic site and traps the NAD+.

2023-03-11 | PXD033100 | Pride

Receptors are affected by selection with each Bacillus thuringiensis israelensis Cry toxin but not with the full Bti mixture in Aedes aegypti

Project description:Bacillus thuringiensis israelensis (Bti) toxins are increasingly used for mosquito control, but little is known about the precise mode of action of each of these toxins, and how they interact to kill mosquito larvae. By using RNA sequencing, we investigated change in gene transcription level and polymorphismvariations associatedwith resistance to each Bti Cry toxin and to the full Bti toxin mixture in the dengue vector Aedes aegypti. The upregulation of genes related to chitin metabolismin all selected strain suggests a generalist, non-toxin-specific response to Bti selection in Aedes aegypti. Changes in the transcription level and/or protein sequences of several putative Cry toxin receptors (APNs, ALPs, α-amylases, glucoside hydrolases, ABC transporters) were specific to each Cry toxin. Selective sweeps associated with Cry4Aa resistancewere detected in 2 ALP and 1 APNgenes. The lack of selection of toxin-specific receptors in the Bti-selected strain supports the hypothesis that Cyt toxin acts as a receptor for Cry toxins in mosquitoes.

2019-05-16 | E-MTAB-7970 | biostudies-arrayexpress

Mechanism of gene regulation by a Staphylococcus aureus toxin

Project description:Virulence of many bacterial pathogens, including the important human pathogen Staphylococcus aureus, depends on the secretion of frequently high amounts of toxins. Toxin production involves the need for the bacteria to make physiological adjustments for energy conservation. While toxins are primarily known to be targets of gene regulation, such changes may be accomplished by regulatory functions of the toxins themselves. However, mechanisms by which toxins regulate gene expression have remained poorly understood. We show here that the phenol-soluble modulin toxins have gene regulatory functions, which in particular include regulation of their own export by direct interference with a GntR-type repressor protein. This capacity was most pronounced in PSMs with low cytolytic capacity, demonstrating functional specification among closely related members of that toxin family. Our study presents a paradigmatic example of how bacterial toxins may regulate gene expression to adapt to the physiological needs in situations of enhanced toxin production.

2016-12-19 | GSE72878 | GEO

Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae

Project description:Pandemic and endemic strains of Vibrio cholerae arise from toxigenic conversion by the CTXφ bacteriophage, a process by which CTXφ infects non-toxigenic strains of V. cholerae. CTXφ encodes the cholera toxin, an enterotoxin responsible for the watery diarrhea associated with cholera infections. Despite the critical role of CTXφ during infections, signals that affect CTXφ-driven toxigenic conversion or expression of the CTXφ-encoded cholera toxin remain poorly characterized, particularly in the context of the gut mucosa. Here, we identify mucin polymers as potent regulators of CTXφ-driven pathogenicity in V. cholerae. Our results indicate that mucin-associated O-glycans block toxigenic conversion by CTXφ and suppress the expression of CTXφ-related virulence factors, including the toxin co-regulated pilus and cholera toxin, by interfering with the TcpP/ToxR/ToxT virulence pathway. By synthesizing individual mucin glycan structures de novo, we identify the Core 2 motif as the critical structure governing this virulence attenuation. Overall, our results highlight a novel mechanism by which mucins and their associated O-glycan structures affect CTXφ-mediated evolution and pathogenicity of V. cholerae, underscoring the potential regulatory power housed within mucus.

2022-12-01 | GSE213598 | GEO

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

Gene expression of early memory and effector precursor CD8 T cells generated by differential TCR signaling strength

Project description:Asymmetric cell division (ACD) and the strength of initial T cell receptor (TCR) signaling are both implied to contribute to the establishment of cellular heterogeneity and CD8 T cell effector and memory differentiation. However, on a single cell level it remained unclear whether ACD generates progeny of different fates and whether the strength of TCR signaling affects this mechanism. Therefore, we developed experimental systems allowing monitoring the fate of single daughter cell progenies derived from an ACD either induced by weak or strong TCR stimulation by in vitro live imaging. We used the combinatorial expression of TCF1 and CD62L as markers indicating fate specification a few days after activation and analyzed the transcriptional profiles of in vitro generated CD62L+TCF1+ and CD62L-TCF1- cells derived from either antibody-induced (AB) activation or from gp33 (high affinity) or C6 (low affinity) peptide stimulation and compared them to in vivo generated effector and memory cells, respectively. Therefore, we sorted CD62L+TCF1+ and CD62L-TCF1- cells on day 6 post activation, followed by bulk RNA sequencing and found that CD62L+TCF1+ cells transcriptionally resembled in vivo generated memory cells, whereas CD62L-TCF1- cells were similar to in vivo generated effector cells.

2023-02-17 | E-MTAB-12563 | biostudies-arrayexpress

Human colon epithelial treated with Clostridium difficile Toxins A and B

Project description:Toxin A and B from Clostridium difficile are the primary virulence factors in Clostridium difficile disease. The changes in gene transcription of human colon epithelial cells were investigated in vitro in order to better understand the many effects of both toxins. HCT-8 cells were treated with 100 ng/ml of either Toxin A or B (TcdA or TcdB). RNA was isolated 2, 6, and 24 hours after addition of toxin from untreated and toxin-treated cells.

2012-01-06 | E-GEOD-29008 | biostudies-arrayexpress

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