Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mycobacterium tuberculosis Rv0102-regulated copper uptake facilitates bacterial escape from phagolysosome

ABSTRACT: The host restricts Mycobacterium tuberculosis (Mtb) access of transition metal ions to inhibit its growth. Cu is essential for the survival of Mtb, but Cu excess is toxic. During co-evolution, Mtb has developed various mechanisms to maintain copper homeostasis. In this report, we firstly found Mtb Rv0102 encoded membrane protein is critical for Mycobacterium Cu uptake. The intracellular Cu level of M. smegmatis (Ms) Rv0102 homolog MSMEG_4702 knockout strain decreased threefold than the wild type, the deletion mutant was more tolerant to higher Cu level. This indicates that Rv0102 is significant for Cu homeostasis and resistance to Cu toxicity. Knocking out the homologous gene MMAR_0267 in M. marinum (Mm) also enhanced its virulence in zebrafish and improved its survival within macrophages. In THP-1 cells infected with Mm, Mm MMAR_0267 deletion mutants’ intracellular survival increased fourfolds and accompanied by less cell apoptosis. Cu deficiency down-regulates the transcription of the M. marinum virulence factor CFP-10, dampening the STING cytosolic signaling in macrophages, fewer IFN-β and less cell apoptosis. These results suggest that Cu is an important factor in inducing cell apoptosis. In summary, mycobacteria can effectively counteract the host's early key nutritional immune mechanisms by regulating copper metabolism, to increase its virulence.

ORGANISM(S): Danio rerio

PROVIDER: GSE235754 | GEO | 2023/06/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A novel copper-responsive regulon in Mycobacterium tuberculosis.

Project description:In this study, we report the identification of a five-locus copper-inducible regulon in Mycobacterium tuberculosis. The identification of a copper responsive regulon unique to pathogenic Mycobacteria suggests copper homeostasis must be maintained during an infection. WT and mutant Mtb cells were grown in Sauton's minimal media to early stationary phase (OD580 = 1.5) and treated with 500 mM copper sulfate (CuSO4) for four hours or the absence

2010-10-27 | E-GEOD-23498 | biostudies-arrayexpress

A Novel Copper Responsive Regulon in Mycobacterium tuberculosis strains mpA and pafA

Project description:In this study, we report the identification of a five-locus copper-inducible regulon in Mycobacterium tuberculosis. The identification of a copper responsive regulon unique to pathogenic Mycobacteria suggests copper homeostasis must be maintained during an infection. WT and mutant Mtb cells were grown in Sauton’s minimal media to early stationary phase (OD580 = 1.5) and treated with 500 mM copper sulfate (CuSO4) for four hours or the absence.

2011-11-01 | E-GEOD-24968 | biostudies-arrayexpress

Proteomic Analysis of Drug-resistant Mycobacteria

Project description:Tuberculosis, caused by the pathogen Mycobacterium tuberculosis is a worldwide public health threat. Mycobacterium tuberculosis is capable of resisting of various stresses in host cells including high levels of ROS and copper ions. To better understand the resistance mechanisms of mycobacteria to copper, we generated a copper-resistant strain of Mycobacterium smegmatis, mc2155-Cu from the selection of copper sulfate treated-bacteria. The mc2155-Cu strain has the 5-fold higher resistance to copper sulfate and the 2-fold higher resistance to isoniazid (INH) than its parental strain mc2155, respectively. Quantitative proteomics was carried out to find differentially expressed proteins between mc2155 and mc2155-Cu. Among 345 differentially expressed proteins, copper-translocating P-type ATPase was up-regulated, while all other ABC transporters were down-regulated in mc2155-Cu, suggesting copper-translocating P-type ATPase plays a crucial role in copper resistance. Results also indicated that the down-regulation of metabolic enzymes and decreases in cellular NAD, FAD, mycothiol, and glutamine levels in mc2155-Cu were responsible to its slow growth rate as compared to mc2155. Down-regulation of KatG2 expression in both protein and mRNA levels indicates the co-evolution of copper and INH resistance in copper resistance bacteria, and provides new evidences to understanding of the molecular mechanisms of survival of mycobacteria under stress conditions.

2016-04-13 | PXD001989 | Pride

Mycobacterium tuberculosis cording in lymphatic endothelial cells (hLEC)

Project description:Mycobacterium tuberculosis (Mtb) displayed cording phenotypes during intracellular infection. RNA-Seq was used to identify transcriptional programmes expressed by hLEC that actviates pathways relating to cellular pro-survival and cyosolic surveillance of intracellular Mtb. Mtb cording was found to be a mechanism to evade xenophagy in the cytosol of endothelial cells.

2020-06-04 | GSE110564 | GEO

Sensing of mycobacterial arabinogalactan by galectin-9 exacerbates mycobacterial infection by inducing matrix metalloproteinases

Project description:Mycobacterial arabinogalactan (AG) is an essential cell wall component of Mycobacteria and a frequent structural and bio-synthetical target for anti-tuberculosis (TB) drug development. Yet, it is unclear whether mycobacterial AG is a pathogen-associated molecular pattern (PAMP) with an elusive pattern recognition receptor (PRR). Here, we report that mycobacterial AG is recognized by galectin-9 and exacerbates mycobacterial infection. Administration of AG-specific aptamers inhibited cellular infiltration caused by Mycobacterium tuberculosis (Mtb) or Mycobacterium bovis BCG, and moderately increased survival of Mtb-infected mice or Mycobacterium marinum-infected zebrafish. AG interacted with carbohydrate recognition domain (CRD) 2 of galectin-9 with high affinity, and galectin-9 associated with transforming growth factor β-activated kinase 1 (TAK1) via CRD2 to trigger subsequent activation of extracellular signal-regulated kinase (ERK) as well as induction of the expression of matrix metalloproteinases (MMPs). Moreover, deletion of galectin-9 or inhibition of MMPs blocked AG-induced pathological impairments in the lung, and the AG-galectin-9 axis aggravated the process of Mtb infection in mice. These results demonstrate that AG is an important virulence factor of mycobacteria and galectin-9 is a novel receptor for Mtb and other mycobacteria, paving the way for the development of novel effective TB immune modulators.

2021-02-17 | GSE166850 | GEO

A new structural paradigm in copper resistance in a human pathogen

Project description:Copper is essential for both innate and adaptive immune function and copper resistance has emerged as an important determinant of virulence of microbial pathogens. In the human pathogen Streptococcus pneumoniae (Spn), cytoplasmic copper resistance is mediated by an operon encoding the copper-responsive repressor CopY, CupA, of unknown function, and CopA, a copper effluxing P1B-type ATPase. We show that CupA is a novel cell membrane-anchored Cu(I) chaperone for CopA, and that a Cu(I)-binding competent, membrane-localized CupA, like CopA, is obligatory for copper resistance.

2013-05-24 | GSE39176 | GEO

The global transcriptional profile of Mycobacterium tuberculosis during human macrophages infection

2007-12-18 | GSE6209 | GEO

The loss of the PDIM/PGL virulence lipids causes differential secretion of ESX-1 sub-strates in Mycobacterium marinum

Project description:Raw and processed files in support of manuscript The loss of the PDIM/PGL virulence lipids causes differential secretion of ESX-1 sub-strates in Mycobacterium marinum The Virulence Lipid PDIM/PGL is essential for optimal protein secretion in Mycobacte-rium marinum WT, PDIM and complement strains lysate and culture filtrate analysis of proteomes

2023-12-21 | MSV000093713 | MassIVE

The global transcriptional profile of Mycobacterium tuberculosis during human macrophages infection

Project description:During lung infection Mycobacterium tuberculosis (Mtb) resides in macrophages and subverts the bactericidal mechanisms of these professional phagocytes. In this work we have analyzed by DNA microarray technique the global transcription profile of Mtb infecting primary human macrophages in order to identify putative bacterial pathogenic factors that can be relevant for the intracellular survival of Mtb. Keywords: time course We compared the global gene expression of the H37Rv strain of Mtb after 4 hours and 24 hours of infection of human macrophage-like THP-1 cells with the gene expression profile of the strain growing exponentially in broth cultures.

2010-05-27 | E-GEOD-6209 | biostudies-arrayexpress

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

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