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Time-resolved dual RNA-seq reveals extensive rewiring of lung epithelial and pneumococcal transcriptomes during early infection

ABSTRACT: Time-resolved dual RNA-seq reveals extensive rewiring of lung epithelial and pneumococcal transcriptomes during early infection

OTHER RELATED OMICS DATASETS IN: GSE79595

PROVIDER: PRJNA316337 | ENA |

REPOSITORIES: ENA

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Time-resolved dual RNA-seq reveals extensive rewiring of lung epithelial and pneumococcal transcriptomes during early infection

Project description:BACKGROUND: Streptococcus pneumoniae, the pneumococcus, is the main etiological agent of pneumonia. Pneumococcal infection is initiated by bacterial adherence to lung epithelial cells. The exact transcriptional changes occurring in both host and microbe during infection are unknown. Here, we developed a time-resolved infection model of human lung alveolar epithelial cells by S. pneumoniae and assess the resulting transcriptome changes in both organisms simultaneously by using dual RNA-seq. RESULTS: Functional analysis of the time-resolved dual RNA-seq data identifies several features of pneumococcal infection. For instance, we show that the glutathione-dependent reactive oxygen detoxification pathway in epithelial cells is activated by reactive oxygen species produced by S. pneumoniae. Addition of the antioxidant resveratrol during infection abates this response. At the same time, pneumococci activate the competence regulon during co-incubation with lung epithelial cells. By comparing transcriptional changes between wild-type encapsulated and mutant unencapsulated pneumococci, we demonstrate that adherent pneumococci, but not free-floating bacteria, repress innate immune responses in epithelial cells including expression of the chemokine IL-8 and the production of antimicrobial peptides. We also show that pneumococci activate several sugar transporters in response to adherence to epithelial cells and demonstrate that this activation depends on host-derived mucins. CONCLUSIONS: We provide a dual-transcriptomics overview of early pneumococcal infection in a time-resolved manner, providing new insights into host-microbe interactions. To allow easy access to the data by the community, a web-based platform was developed ( http://dualrnaseq.molgenrug.nl ). Further database exploration may expand our understanding of epithelial-pneumococcal interaction, leading to novel antimicrobial strategies.

2016-08-26 | GSE79595 | GEO

Dual RNAseq of pneumococcal infection

Project description:Dual RNAseq of pneumococcal infection

| PRJNA553810 | ENA

Time-resolved dual RNA-seq reveals extensive rewiring of lung epithelial and pneumococcal transcriptomes during early infection.

Project description: Not available

| S-EPMC5039909 | biostudies-literature

Dual RNAseq of pneumococcal infection

Project description:Streptococcus pneumoniae is the dominant cause of community-acquired pneumonia world-wide. Invasion of the pleural space is common and results in increased mortality. We set out to determine the bacterial and host factors that influence invasion of the pleural space. In a murine model of pneumococcal infection, we isolated neutrophil-dominated samples of bronchoalveolar and pleural fluid containing bacteria 48 hours after infection. Using dual RNA-seq, we characterised bacterial and host transcripts that were differentially regulated between these compartments and bacteria in broth and resting neutrophils respectively. Pleural and lung samples showed upregulation of genes involved in positive regulation of neutrophil extravasation but down-regulation of genes mediating bacterial killing. Compared to the lung samples, cells within the pleural space showed marked upregulation of many genes induced by type I interferons, cytokines implicated in preventing bacterial transmigration across epithelial barriers. Differences in the bacterial transcripts between the infected samples and bacteria grown in broth showed upregulation of genes in the bacteriocin locus, the pneumococcal surface adhesin PsaA, and the glycopeptide resistance gene, vanZ; the gene encoding the ClpP protease was downregulated in infection. 169 intergenic putative small bacterial RNAs were also identified, of which 43 (25.4%) had been previously described. 42 of the small RNAs were upregulated in pleura compared to broth, including many previously identified as important in virulence. Our results have identified key host and bacterial responses to invasion of the pleural space that can be potentially exploited to develop alternative antimicrobial strategies for prevention and treatment of pneumococcal pleural disease.

2019-07-11 | GSE134118 | GEO

Dual RNA-seq on pneumococcal infection to zebrafish embryo model

Project description:Zebrafish embryo has been emerging as an interesting model of infection due to their fecundity, transparency and availability of genetic tools. Streptococcus pneumoniae, the pneumococcus, is the main etiological agent of pneumonia, sepsis and meningitis. The bacteria expresses a very important virulence factor, pneumolysin able to form pores on cholesterol-based membranes and to activate innate immune system. Here, we exploited the recently described dual RNA-seq to simultaneously measure genome-wide expression of host and pathogen eight hours into infection. Functional enrichment analysis showed certain pathways such as autophagy and apoptosis being activated in the host while stress responses including pneumococcal competence. The study is the first to describe dual RNA-seq application in whole organism sequencing in infection model.

2021-12-14 | GSE123988 | GEO

Dual RNA-seq on pneumococcal infection to murine lung

Project description:Dual RNA-seq on pneumococcal infection to murine lung

| PRJNA510421 | ENA

Dual RNA-seq on pneumococcal infection to murine lung

Project description:Tropism is a very important factor in pneumococcal infection. Previous study has shown that clinical isolate showed niche preference in model organism. In particular, ear isolate showed particular tropism in nasopharyngeal carriage while blood isolate survives better in the murine lung. We have detected a SNP located inside rafR, repressor of sugar metabolism regulon, that contributes to strain tropism. We then perform a swap mutation between the rafR ear and blood isolates and perform intranasal infection using the four strains: original ear and blood isolates, ear isolate with rafR blood isolate and blood isolate with rafR ear isolate. We harvested the lung six hours into infection and exploited the recently described dual RNA-seq to reconstruct transcriptomics landscape during host-pathogen interaction.

2019-12-03 | GSE123982 | GEO

Dual RNA-seq on pneumococcal infection to zebrafish embryo model

Project description:Dual RNA-seq on pneumococcal infection to zebrafish embryo model

| PRJNA510431 | ENA

: Extensive Rewiring of the EGFR Network in Colorectal Cancer Cells Expressing Transforming Levels of KRASG13D

Project description:RAW files of corresponding Baits used in Extensive Rewiring of the EGFR Network in Colorectal Cancer Cells Expressing Transforming Levels of KRASG13D

2019-12-03 | PXD016512 | Pride

Extensive Rewiring of the EGFR Network in Colorectal Cancer Cells Expressing Transforming Levels of KRASG13D

Project description:RAW files of corresponding Baits used in Extensive Rewiring of the EGFR Network in Colorectal Cancer Cells Expressing Transforming Levels of KRASG13D

2019-12-02 | PXD016505 | Pride

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