Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Infection with Chlamydia trachomatis reprograms human cells through inhibition of protein synthesis

ABSTRACT: The obligate intracellular bacterium Chlamydia trachomatis replicates in a cytosolic vacuole in human epithelial cells. Infection of human cells with C. trachomatis causes substantial changes to many host cell signalling pathways but the molecular basis of such influence is not well understood. Studies of gene transcription of the infected cell have shown altered transcription of many host cell genes, indicating a transcriptional response of the host cell to the infection. We here describe that infection of human cells with C. trachomatis as well as infection of murine cells with C. muridarum profoundly inhibits protein synthesis of the infected host cell. This inhibition was accompanied by changes to the ribosomal profile of the infected cell indicative of a block of translation initiation, most likely as part of a stress response. The chlamydial protease CPAF also reduced protein synthesis in uninfected cells although CPAF-deficient C. trachomatis showed no defect in this respect. Analysis of polysomal mRNA as a proxy of actively transcribed mRNA identified a number of biological processes differentially affected by chlamydial infection. Mapping of differentially regulated genes onto a protein interaction network identified nodes of up- and down-regulated networks during chlamydial infection. Proteomic analysis of protein synthesis further suggested translational regulation of host cell functions by chlamydial infection. These results demonstrate reprogramming of the host cell during chlamydial infection through the alteration of protein synthesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE114556 | GEO | 2019/05/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Early transcriptional landscapes of Chlamydia trachomatis-infected epithelial cells at single cell resolution

Project description:Here we examined host cell gene expression in response to Chlamydia trachomatis infection by applying scRNA-Seq to in vitro C. trachomatis-infected HEp-2 epithelial cells and time-matched uninfected cells over the early chlamydial developmental cycle (3, 6 and 12 hours). We collected 264 single cells across both conditions all time points. The aims of the experiment were examining host cell responses to infection at single cell resolution, and identifying early host cell signatures of infection.

2019-11-19 | GSE132525 | GEO

Natural killer cells regulate pulmonary macrophages polarization in host defense chlamydial lung infection

Project description:NK cells and pulmonary macrophages both are important components of innate immunity. The interaction between NK cells and pulmonary macrophages during Chlamydia muridarum（C. muridarum）respiratory infections is poorly understood. In this study, we explored the effect of NK cells on regulation of pulmonary macrophage function during chlamydial lung infection. We found that NK depletion led to polarization of pulmonary macrophages from M1 to M2 phenotype, and this related to significantly reduced miR-155 expression in pulmonary macrophage. Using adoptive transfer approach, we found that the recipient mice receiving lung macrophages isolated from C. muridarum-infected NK-cell-depleted mice exhibited an increased bacterial load and severe inflammation in the lung upon chlamydial challenge when compared with the recipients of lung macrophages from infected IgG -treated mice. Herein, the effects of NK cells on macrophage polarization were examined in vitro. We found that NK cells from chlamydial-infected mice (iNK) significantly induced M1 polarization compared to that from sham-infected mice (uNK). Inhibition of miR-155 expression in macrophages attenuated M1 polarization induced by iNK, while miR-155 over-expression enhanced it. Furthermore, neutralization of IFN-γ in the coculture system decreased the expression of miR-155 by macrophages, and resulted in diminished M1 polarization induced by iNK cells. The data indicates that NK cells direct M1 polarization through up-regulation of miR-155 by IFN-γ production, and NK-regulated macrophage polarization is functionally relevant to host defense against chlamydial infection.

2022-01-26 | GSE183577 | GEO

Chlamydia trachomatis induces the transcriptional activity of host YAP in a Hippo-independent fashion

Project description:The obligate intracellular pathogen Chlamydia trachomatis is the causative agent of the most common bacterial sexually transmitted disease worldwide. While the host response to infection by this pathogen has been well characterized, it remains unclear to what extent host gene expression during infection is the product of Chlamydia-directed modulation of host transcription factors. In this report, we show the transcriptome of Chlamydia-infected epithelial cells exhibits gene expression consistent with activity of YAP, a transcriptional coactivator implicated in cell proliferation, wound healing, and fibrosis. After confirming induction of YAP target genes during infection, we observed increased YAP nuclear translocation in Chlamydia-infected epithelial cells. We further show that increased YAP activation is a Chlamydia-directed process, requiring de novo protein synthesis during midcycle infection. Surprisingly, infection-mediated YAP activation bypasses YAP inhibition by the Hippo kinase cascade, with phosphorylation at S127 remaining unchanged. Instead, phosphorylation at Y357 was increased along with nuclear translocation, indicating that infection overrides phospho-inhibition at S127. Nuclear translocation of Y357F mutant YAP was not increased by infection, demonstrating that chlamydial YAP activation requires phosphorylation at this residue. Taken together, our results define a transcriptome-altering mechanism potentially linked to chlamydial fibrosis and other advanced disease sequelae.

2023-02-13 | GSE180783 | GEO

Chlamydia trachomatis induces the transcriptional activity of host YAP in a Hippo-independent fashion

2023-02-13 | GSE180782 | GEO

Chlamydia trachomatis induces the transcriptional activity of host YAP in a Hippo-independent fashion

2023-02-13 | GSE198272 | GEO

Chromatin accessibility dynamics of Chlamydia-infected epithelial cells

Project description:We applied Formaldehyde-Assisted Isolation of Regulatory Elements enrichment followed by sequencing (FAIRE-Seq) to generate genome-wide temporal chromatin maps of Chlamydia trachomatis-infected human epithelial cells in vitro over the chlamydial developmental cycle. We detected both conserved and distinct temporal regions of chromatin accessibility associated with C. trachomatis infection. The observed differentially accessible chromatin regions, including several Clusters of Open Regulatory Elements (COREs) and temporally-enriched sets of transcription factors, may help shape the host cell response to infection. These regions and motifs were linked to genomic features and genes associated with immune responses, re-direction of host cell nutrients, intracellular signaling, cell-cell adhesion, extracellular matrix, metabolism and apoptosis. This work will serve as a basis for future functional studies of transcriptional regulation and epigenomic regulatory elements in Chlamydia-infected human cells.

2020-10-28 | GSE132448 | GEO

A Unique insight into the MiRNA profile during Genital Chlamydial Infection

Project description:Genital C. trachomatis (CT) infection may cause pelvic inflammatory disease (PID) that can lead to tubal factor infertility (TFI). Understanding the pathogenesis of chlamydial complications including the pathophysiological processes within the female host genital tract is of immense importance in preventing adverse pathology. In this study, we tested the hypothesis that the miRNA profile of a acute primary chlamydial infection characterized by temporary inflammation versus the profile associated with chronic genital chlamydial infections that might precipitate PID or TFI will be different. Thus, we analyzed and compared the differentially expressed miRNAs that regulate CT pathogenesis after a single genital infection and those involved in the development of PID and TFI after repeat infections. Mice (Mus musculus) were infected with Chlamydia muridarum once or twice with a month interval between infections, and then sacrificed and genital tract tissues were collected at 1, 2, 4, and 8 weeks after infection. miRNAs were differentially expressed in both first infection and the re-infection; however, the miRNA expression profile was different for both groups. Pathway analysis showed that, amongst other functions, the differentially regulated miRNA might be regulating several pathways involved in cellular and tissue development, disease conditions and toxicity. Grant number: 1SC2HD086066-03 Funding source: Eunice Kennedy Shriver National Institute of Child Health & Human Development Title: Discovering Novel Biomarkers Predictive of Tubal Infertility Caused by Chlamydia. Principal investigator: Yusuf Omosun Date: 05/01/2015-04/30/2019

2019-01-27 | GSE118396 | GEO

Integrating lncRNAs and mRNAs expression profiles in penicillin-induced persistent chlamydial infection in HeLa cells

Project description:Chlamydia trachomatis (C. trachomatis) is a major etiological agent of sexually transmitted infection. Some stressing conditions can result in persistent chlamydial infection, which is thought to associate with severe complications such as ectopic pregnancy and tubal factor infertility. Long noncoding RNAs (lncRNAs) have been identified as key modulators in many biological processes. However, the role of lncRNAs in persistent chlamydial infection is still unclear. In this study, we used lncRNA and mRNA microarray to identify the global lncRNAs and mRNAs expression in penicillin-induced persistent chlamydial infection in HeLa cells as well as the control group (HeLa cells without C. trachomatis infection). Among 1005 differentially expressed lncRNAs, 585 lncRNAs were upregulated and 420 downregulated in persistent chlamydial infection, while 410 mRNAs were identified to express differentially, of which 113 mRNAs were upregulated and 297 downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with differentially expressed genes were performed. We then constructed the lncRNA-miRNA-mRNA competing endogenous RNAs (ceRNAs) network. Four mRNAs were validated to be changed by quantitative real-time PCR which were correlated with the microarray result. Integration of protein-protein interaction (PPI) network was constructed and hub genes were identified. These findings provide a new perspective on the molecular mechanism of penicillin-induced persistent chlamydial infection.

2022-02-14 | GSE180478 | GEO

Quantitative proteomics of the infectious and replicative forms of Chlamydia trachomatis L2

Project description:The obligate intracellular developmental cycle of Chlamydia trachomatis presents significant challenges in defining its proteome. In this study we have applied quantitative proteomics to both the intracellular reticulate body (RB) and the extracellular elementary body (EB) from C. trachomatis. We used C. trachomatis L2 which is a model chlamydial isolate for such a study since it has a high infectivity: particle ratio and there is an excellent quality genome sequence. EBs and RBs (>99% pure) were quantified by chromosomal and plasmid copy number using PCR to determine the concentrations of chlamydial proteins per bacterial cell. RBs harvested at 15h post infection (PI) were purified by three successive rounds of gradient centrifugation. This is the earliest possible time to obtain purified RBs, free from host cell components in quantity, within the constraints of the technology, EBs were purified at 48h PI. We then used two-dimensional reverse phase UPLC to fractionate RB or EB peptides before mass spectroscopic analysis, providing absolute amount estimates of chlamydial proteins.

2016-06-28 | PXD003025 | Pride

Supermajority of Chlamydia trachomatis genes are activated during the first hour of infection

Project description:The obligate intracellular bacterium Chlamydia has a unique developmental cycle that alternates between two contrasting cell types. With a hardy envelope and highly condensed genome, the small elementary body (EB) maintains limited metabolic activities yet can survive in an extracellular environment and is infectious. After entering host cells, EBs differentiate into larger and proliferating reticulate bodies (RBs). Progeny EBs are derived from RBs in late developmental stages and eventually exit host cells. How the expression of the chlamydial genome consisting of nearly 1000 genes governs the chlamydial developmental cycle is unclear. A previous microarray study identified only 29 immediately early genes, defined as genes activated by the first hour postinoculation, in C. trachomatis. By performing RNA sequencing analysis for C. trachomatis cultures with high multiplicities of infection (i.e., MOI of 50 and 200), we observed that 730 C. trachomatis genes underwent 2- to 900-fold activation within one hour postinoculation. By conducting quantitative reverse transcription real-time PCR (qRT-PCR) analysis for 48 of the 730 genes using an MOI of 1, we confirmed the expression increases in 46 genes. Our results demonstrate that the immediate early transcriptome is tens of times more extensive than previously realized. Gene ontology analysis indicates that the activation spans across all functional categories. We conclude that a supermajority of the C. trachomatis genes are activated almost immediately after EBs are inside host cells to initiate the differentiation toward RBs and to establish an intracellular niche conducive for chlamydial development and growth. RNA-Seq analysis was performed for Chlamydia trachomatis L2

2024-01-30 | GSE248988 | 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