Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Secretome and intracellular proteome of eccE1 and mycP1 deletion mutants of Mycobacterium tuberculosis

ABSTRACT: Mycobacterium tuberculosis uses the specialised ESX-1 secretion system to secrete virulence factors and potent immunogenic effectors required for disease progression. ESX-1 is a multi-subunit apparatus with a membrane complex that is predicted to form a pore in the cytoplasmic membrane. In M. tuberculosis this complex is composed of five membrane proteins: EccB1, EccCa1, EccCb1, EccD1, EccE1. In this study, we have characterised the membrane component EccE1, and we found that deletion of eccE1 leads to destabilisation of EccB1, EccCa1 and EccD1 levels as well as to the disruption of EsxA, EsxB, EspA and EspC secretion. Surprisingly, secretion of EspB was not affected by loss of EccE1.

INSTRUMENT(S): LTQ Orbitrap XL

ORGANISM(S): Mycobacterium Tuberculosis

TISSUE(S): Cell Culture, Cell Line Cell

DISEASE(S): Pulmonary Tuberculosis

SUBMITTER: Andrej Benjak

LAB HEAD: Stewart Thomas Cole

PROVIDER: PXD012584 | Pride | 2019-12-16

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	OxidationMSites.txt	Txt
	PS_180605_HF_A.raw	Raw
	PS_180605_HF_AA.raw	Raw
	PS_180605_HF_AB.raw	Raw
	PS_180605_HF_B.raw	Raw

Items per page:

1 - 5 of 36

Similar Datasets

Secretome and intracellular proteome of espB deletion mutant of Mycobacterium tuberculosis

Project description:Mycobacterium tuberculosis relies on the ESX-1 secretion system for survival, multiplication in and escape from macrophages. In this work we investigate the role of the EspB protein, encoded within the esx-1 gene cluster, in virulence and ESX-1 substrate secretion in M. tuberculosis H37Rv. Genetic, proteomic and immunological data show that, contrary to previous reports, an espB knock-out mutant is only partially attenuated in ex vivo infection models, where EsxA, EsxB and EspC antigen presentation is not affected, and secretes the major virulence factor EsxA. Additionally, we demonstrate that EspB does not require an intact and functional ESX-1 apparatus for being secreted in H37Rv and in M. bovis BCG, as opposed to other strains such as CDC1551 and Erdman, thereby suggesting that other ESX systems may be involved in the process. Overall our findings highlight unexplored differences in the secretion profiles of various mycobacterial strains and underscore the plasticity of ESX-dependent secretion in mycobacteria.

2021-09-24 | PXD016565 | Pride

Mass-spectrometry-based analysis of the secretome of M. tuberculosis mutants

2018-12-10 | PXD011466 | Pride

espB deletion mutant of Mycobacterium tuberculosis

2021-09-24 | PXD011475 | Pride

espL deletion mutant of Mycobacterium tuberculosis

Project description:The ESX-1, type VII, secretion system represents the major virulence determinant of Mycobacterium tuberculosis, one of the most successful intracellular pathogens. Here, by combining genetic and high-throughput approaches, we show that EspL, a protein of 115 amino acids, is essential for mediating ESX-1-dependent virulence and for stabilization of EspE, EspF and EspH protein levels. Indeed, an espL knock-out mutant was unable to replicate intracellularly, secrete ESX-1 substrates or stimulate innate cytokine production. Moreover, proteomic studies detected greatly reduced amounts of EspE, EspF and EspH in the espL mutant as compared to the wild type strain, suggesting a role for EspL as a chaperone. The latter conclusion was further supported by discovering that EspL interacts with EspD, which was previously demonstrated to stabilize the ESX-1 substrates and effector proteins, EspA and EspC. Moreover, loss of EspL also leads to downregulation in M. tuberculosis of WhiB6, a redox-sensitive transcriptional activator of ESX-1 genes. Overall, our data highlight the importance of a so-far overlooked, though conserved, component of the ESX-1 secretion system and begin to delineate the role played by EspE, EspF and EspH in virulence and host-pathogen interaction.

2018-12-10 | PXD010929 | Pride

Characterization of ESX-1 components EccA1, EspG1 and EspH reveal pivotal role of Esp substrates in the Mycobacterium marinum infection cycle

Project description:The pathogen Mycobacterium tuberculosis employs a range of ESX-1 substrates to manipulate the host and build a successful infection. Although the importance of ESX-1 secretion in virulence is well established, the characterization of its individual components and the role of individual substrates is far from complete. Here, we describe the functional characterization of the accessory ESX-1 proteins EccA1, EspG1 and EspH, i.e. proteins that are not present in all five ESX system of mycobacteria. Proteomic analysis revealed that EspG1 is crucial for ESX-1 secretion, since all detectable ESX-1 substrates were absent from the cell surface and culture supernatant in an espG1 mutant. Deletion of eccA1 resulted in minor secretion defects, but interestingly, the severity of these secretion defects was dependent on the culture conditions. Finally, espH deletion showed a partial secretion defect, only secretion of EspE, EspF and EsxA/EsxB was blocked.

2018-08-02 | PXD008905 | Pride

Transcriptional profile of Mycobacterium tuberculosis mycP1-eccE1 deletion mutant

Project description:Mycobacterium tuberculosis is a slow-growing intracellular bacterium with the ability to induce host cell death and persist indefinitely in the human body. This pathogen uses the specialised ESX-1 secretion system to secrete virulence factors and potent immunogenic effectors required for disease progression. ESX-1 is a multi-subunit apparatus with a membrane complex that is predicted to form a pore in the cytoplasmic membrane. In M. tuberculosis this complex is made of five membrane proteins: EccB1, EccCa1, EccCb1, EccD1, EccE1. In this study, we have characterised the membrane component EccE1, and we found that deletion of eccE1 leads to disruption of ESX-1 secretion and attenuation of M. tuberculosis ex vivo.

2019-09-01 | GSE119582 | GEO

A novel phenotypic drug screen identifies potent inhibitors of mycobacterial virulence protein secretion

Project description:Mycobacterium tuberculosis (Mtb) depends on protein secretion systems for intracellular survival and virulence. The major virulence determinant and ESX-1 dependent effector protein EsxA causes tissue damage and necrosis which promotes spread and dissemination of the bacterium. We developed a fibroblast survival assay (FSA) that exploits this phenotype by selecting for molecules that protect host cells from Mtb-induced lysis. Hit compounds identified in this high-throughput screen blocked the secretion of EsxA thus promoting phagosome maturation which led to substantially reduced bacterial burden in activated macrophages. Target identification studies performed on these drugs led to discovery of a benzothiophene containing histidine kinase inhibitor and a benzyloxybenzylidine hydrazine compound affecting mycobacterial metal ion homeostasis which enabled us to reveal zinc stress as a signal for EsxA secretion. Collectively, this novel drug screening approach can help to tackle the mounting problem of antibiotic-resistant mycobacteria by largely extending the target spectrum of small molecule libraries.

2015-05-15 | GSE58314 | GEO

Proteomic analysis of the secretome of a esxaA mutant Mycobacterium tuberculosis strain

Project description:Extracellular Mycobacterium tuberculosis (Mtb) aggregates can evade phagocytosis and intracellular host-cell defenses by inducing macrophage killing. We showed that Mtb aggregates require a functional ESX-1 type VII secretion system to induce cell death upon contact with macrophages. We used quantitative proteomics to compare the secretome of a esxA mutant strain with the wild type reference to identify secreted bacteria factors involved in macrophage death induction.

2023-03-16 | PXD035082 | Pride

Immunopeptidomics reveals determinants of Mycobacterium tuberculosis antigen presentation on MHC class I (SureQuant data)

Project description:CD8+ T cells contribute to protective immunity to Mycobacterium tuberculosis (Mtb), but the principles that govern presentation of Mtb peptides on MHC class I (MHC-I) on the surface of infected macrophages for CD8+ T cell recognition are incompletely understood. Here, we use internal standard parallel reaction monitoring (IS-PRM, also known as SureQuant) to rigorously validate identifications of Mtb-derived MHC-I peptides obtained in data-dependent MS analyses. We further use SureQuant to quantify presentation of Mtb peptides derived from the secreted effector proteins EsxA and EsxJ across multiple experimental conditions. We show that presentation of both EsxA- and EsxJ-derived peptides requires the activity of the mycobacterial ESX-1 type VII secretion system, possibly indicating that ESX-1-mediated phagosome membrane damage allows Mtb proteins to access MHC-I antigen processing pathways. We show that this requirement is independent of type I interferon signaling that occurs downstream of phagosome damage. Treatment with inhibitors of conventional proteolytic pathways involved in MHC-I antigen processing inhibits presentation of self peptides as expected, but does not inhibit presentation of Mtb peptides, implying an alternative or redundant mechanism of processing.

2023-04-24 | PXD037843 | Pride

Gene expression profile of M.tuberculosis espR (Rv3849) mutant

Project description:Mycobacterium tuberculosis, a pathogen of global importance, utilizes the ESX-1 protein secretion system to export virulence factors that disarm host macrophages. Although this secretory pathway is critical for virulence, how ESX-1 is regulated is completely unknown. Here we show that EspR (Rv3849) is a key regulator of ESX-1. EspR activates transcription of an operon that includes three ESX-1 components, Rv3616c-Rv3614c, whose expression in turn promotes secretion of ESX-1 substrates. Keywords: Strain comparison Comparison of the global gene expression of three M.tb strains grown in log phase: Erdman strain of M.tb, espR transposon mutant, and the espR transposon mutant complemented with the espR gene

2008-07-04 | E-GEOD-11696 | 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