An advanced intestinal tissue model reveals host and pathogen strategies during Salmonella infection
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA563323 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10056100.fastq.gz | Fastqsanger.gz | |||
| SRR10056101.fastq.gz | Fastqsanger.gz | |||
| SRR10056102.fastq.gz | Fastqsanger.gz | |||
| SRR10056103.fastq.gz | Fastqsanger.gz | |||
| SRR10056104.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:Here, we introduce an intestinal tissue model to study human enteric infections. Our model comprises epithelial and endothelial layers, a primary intestinal collagen scaffold, and immune cells. We use Dual RNA-seq to chart the communication amongst several different cell types at the intestinal barrier and the pathogen. The results suggest that Salmonella uses its type III secretion systems to manipulate STAT3-dependent inflammatory responses locally in the epithelial compartment. Our approach promises to reveal more human-specific infection strategies employed by Salmonella and other pathogens.
2020-01-20 | GSE136717 | GEO
Project description:A major obstacle in infection biology is the limited ability to recapitulate human disease trajectories in traditional cell culture and animal models, which impedes the translation of basic research into clinics. Here, we introduce a three-dimensional (3D) intestinal tissue model to study human enteric infections at a level of detail that is not achieved by conventional two-dimensional monocultures. Our model comprises epithelial and endothelial layers, a primary intestinal collagen scaffold, and immune cells. Upon Salmonella infection, the model mimics human gastroenteritis, in that it restricts the pathogen to the epithelial compartment, an advantage over existing mouse models. Application of dual transcriptome sequencing to the Salmonella-infected model revealed the communication of epithelial, endothelial, monocytic, and natural killer cells among each other and with the pathogen. Our results suggest that Salmonella uses its type III secretion systems to manipulate STAT3-dependent inflammatory responses locally in the epithelium without accompanying alterations in the endothelial compartment. Our approach promises to reveal further human-specific infection strategies employed by Salmonella and other pathogens.IMPORTANCE Infection research routinely employs in vitro cell cultures or in vivo mouse models as surrogates of human hosts. Differences between murine and human immunity and the low level of complexity of traditional cell cultures, however, highlight the demand for alternative models that combine the in vivo-like properties of the human system with straightforward experimental perturbation. Here, we introduce a 3D tissue model comprising multiple cell types of the human intestinal barrier, a primary site of pathogen attack. During infection with the foodborne pathogen Salmonella enterica serovar Typhimurium, our model recapitulates human disease aspects, including pathogen restriction to the epithelial compartment, thereby deviating from the systemic infection in mice. Combination of our model with state-of-the-art genetics revealed Salmonella-mediated local manipulations of human immune responses, likely contributing to the establishment of the pathogen's infection niche. We propose the adoption of similar 3D tissue models to infection biology, to advance our understanding of molecular infection strategies employed by bacterial pathogens in their human host.
| S-EPMC7029144 | biostudies-literature
Project description:The potential for commensal microorganisms indigenous to a host (the microbiome or microbiota) to alter infection outcome by influencing host-pathogen interplay is largely unknown. We used a multi-omics systems approach, incorporating proteomics, metabolomics, glycomics, and metagenomics, to explore the molecular interplay between the murine host, the pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), and commensal gut microorganisms during intestinal infection with S. Typhimurium. We find proteomic evidence that S. Typhimurium thrives within the infected 129/SvJ mouse gut without antibiotic pre-treatment, inducing inflammation and disrupting the intestinal microbiome (e.g., suppressing Bacteroidetes and Firmicutes while promoting growth of Salmonella and Enterococcus). Alteration of the host microbiome population structure was highly correlated with gut environmental changes, including the accumulation of metabolites normally consumed by commensal microbiota. Finally, the less characterized phase of S. Typhimuriums lifecycle was investigated, and both proteomic and glycomic evidence suggests S. Typhimurium may take advantage of increased fucose moieties to metabolize fucose while growing in the gut. The application of multiple omics measurements to Salmonella-induced intestinal inflammation provides insights into complex molecular strategies employed during pathogenesis between host, pathogen, and the microbiome.
2014-06-25 | ST000083 | MetabolomicsWorkbench
Project description:The potential for commensal microorganisms indigenous to a host (the microbiome or microbiota) to alter infection outcome by influencing host-pathogen interplay is largely unknown. We used a multi-omics systems approach, incorporating proteomics, metabolomics, glycomics, and metagenomics, to explore the molecular interplay between the murine host, the pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), and commensal gut microorganisms during intestinal infection with S. Typhimurium. We find proteomic evidence that S. Typhimurium thrives within the infected 129/SvJ mouse gut without antibiotic pre-treatment, inducing inflammation and disrupting the intestinal microbiome (e.g., suppressing Bacteroidetes and Firmicutes while promoting growth of Salmonella and Enterococcus). Alteration of the host microbiome population structure was highly correlated with gut environmental changes, including the accumulation of metabolites normally consumed by commensal microbiota. Finally, the less characterized phase of S. Typhimurium's lifecycle was investigated, and both proteomic and glycomic evidence suggests S. Typhimurium may take advantage of increased fucose moieties to metabolize fucose while growing in the gut. The application of multiple omics measurements to Salmonella-induced intestinal inflammation provides insights into complex molecular strategies employed during pathogenesis between host, pathogen, and the microbiome.
2014-06-24 | MTBLS96 | MetaboLights
Project description:Physical forces associated with spaceflight and spaceflight analogue culture regulate a wide range of physiological responses by both bacterial and mammalian cells that can impact infection. However, our mechanistic understanding of how these environments regulate host-pathogen interactions in humans is poorly understood. Using a spaceflight analogue low fluid shear culture system, we investigated the effect of Low Shear Modeled Microgravity (LSMMG) culture on the colonization of Salmonella Typhimurium in a 3-D biomimetic model of human colonic epithelium containing macrophages. RNA-seq profiling of stationary phase wild type and hfq mutant bacteria alone indicated that LSMMG culture induced global changes in gene expression in both strains and that the RNA-binding protein Hfq played a significant role in regulating the transcriptional response of the pathogen to LSMMG culture. However, a core set of genes important for adhesion, invasion, and motility were commonly induced in both strains. LSMMG culture enhanced the colonization (adherence, invasion and intracellular survival) of Salmonella in this advanced model of intestinal epithelium using a mechanism that was independent of Hfq. Although S. Typhimurium hfq mutants are normally defective for invasion when grown as conventional shaking cultures, LSMMG conditions unexpectedly enabled high levels of colonization by an isogenic hfq mutant. In response to infection with either the wild type or mutant, host cells upregulated transcripts involved in inflammation, tissue remodeling, and wound healing during intracellular survival. Interestingly, infection by the hfq mutant led to fewer transcriptional differences between LSMMG- and control-infected host cells relative to infection with the wild type strain. This is the first study to investigate the effect of LSMMG culture on the interaction between S. Typhimurium and a 3-D model of human intestinal tissue. These findings advance our understanding of how physical forces can impact the early stages of human enteric salmonellosis.
2022-05-17 | GSE146347 | GEO
Project description:Infections by the fungus Monilinia laxa, the main cause of brown rot in Europe, result in considerable losses of stone fruit. Herein, we present a comprehensive transcriptomic approach to unravel strategies deployed by nectarine fruit and M. laxa during their interaction. We used M. laxa-inoculated immature and mature fruit, which were resistant and susceptible to brown rot, respectively, to perform a dual RNA-seq analysis. In immature fruit, host responses, pathogen biomass, and pathogen transcriptional activity peaked at 14 – 24 hours post inoculation (hpi), at which point M. laxa appeared to switch its transcriptional response to either quiescence or death. Mature fruit experienced an exponential increase in host and pathogen activity beginning at 6 hpi. Functional analyses in both host and pathogen highlighted differences in stage-dependent strategies. For example, in immature fruit, M. laxa unsuccessfully employed carbohydrate-active enzymes (CAZymes) for penetration, which the fruit was able to combat with tightly regulated hormone responses and an oxidative burst that challenged the pathogen’s survival at later time points. In contrast, in mature fruit, M. laxa was more dependent on proteolytic effectors than CAZymes and was able to invest in filamentous growth early during the interaction. Hormone analyses of mature fruit infected with M. laxa indicated that, while jasmonic acid activity was likely useful for defense, high ethylene activity may have promoted susceptibility through induction of ripening processes. Lastly, we identified M. laxa genes that were highly induced in both quiescent and active infections and may serve as targets for control of brown rot.
2020-08-01 | GSE146293 | GEO
Project description:Host-pathogen co-evolutionary dynamics force microbial plant pathogens to constantly develop and adjust specific adaptations to thrive in their plant host, and therefore also act as strong drivers of divergence and speciation in pathogens. Factors that confer host specialization and determine host specificity are very diverse and range from molecular and morphological strategies to metabolic and reproductive adaptations. Identification of these key factors is a major goal in the study of pathogen evolution and may aid the development of sustainable crops and crop protection strategies. We here took a novel experimental approach and conducted comparative microscopy and transcriptome analyses of the closely related, recently diverged fungal pathogens Zymoseptoria tritici, Z. pseudotritici, and Z. ardabiliae that establish compatible and incompatible interactions with wheat. Although infections of the incompatible species induce plant defense response during invasion of stomatal openings, we found a highly conserved early-infection program among the three species. The transcriptional programs of the three pathogens are conserved to a large extent, as only 9.2% of the 8,885 orthologous genes are significantly differentially expressed during initial infection of wheat. The genes up-regulated in the compatible pathogen reflect adaptation to growth in wheat tissue e.g., by re-programming of fungal metabolism. In contrast, genes primarily involved in counteracting cell stress and damage are strongly induced in the incompatible species. Based on the species-specific gene expression profiles, we further identified nine candidate genes encoding putative effectors and host-specificity determinants in Z. tritici. These effectors are strongly induced in the compatible species and may interfere with host immune suppression. We also identify putative necrotrophic effectors which are induced at the onset of necrotrophic growth. Together, the results presented here indicate that host specialization has involved transcriptional adaptation of a relatively small number of genes. Our findings demonstrate the potential comparative analyses of compatible and incompatible infections present for identifying traits involved in pathogen evolution and host specialization.
2023-07-25 | GSE237842 | GEO
Project description:Elucidation of host-pathogen interaction is essential for developing effective strategies to combat bacterial infection. Dual RNA-Seq using cultured cells or tissues/organs as the pathogen host has emerged as a novel strategy to understand the response concurrently from both pathogen and host at cellular level. However, bacterial infection mostly causes systematic responses from the host at organism level where the interplay is urgently to be understood but inevitably being neglected by the current practice. Here, we developed an approach that simultaneously monitor the genome-wide infection-linked transcriptional alterations in both pathogenic Vibrio parahaemolyticus and the infection host nematode Caenorhabditis elegans. Besides the dynamic alterations in both transcriptomes of C. elegans and V. parahaemolyticus during infection, we identify a two-component system, BarA/UvrY, that are essential for host colonization. BarA/UvrY not only controls the virulence factors in V. parahaemolyticus including Type III and Type VI secretion systems, but also represses the MAP kinase mediated signaling cascades to attenuate innate immune responses. Thus, our study exemplifies the use of dual RNA-Seq at organism level to uncover previously unrecognized interplay between host and pathogen.
2020-09-10 | GSE138199 | GEO
Project description:The potential for commensal microorganisms indigenous to a host (the 'microbiome' or 'microbiota') to alter infection outcome by influencing host-pathogen interplay is largely unknown. We used a multi-omics "systems" approach, incorporating proteomics, metabolomics, glycomics, and metagenomics, to explore the molecular interplay between the murine host, the pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), and commensal gut microorganisms during intestinal infection with S. Typhimurium. We find proteomic evidence that S. Typhimurium thrives within the infected 129/SvJ mouse gut without antibiotic pre-treatment, inducing inflammation and disrupting the intestinal microbiome (e.g., suppressing Bacteroidetes and Firmicutes while promoting growth of Salmonella and Enterococcus). Alteration of the host microbiome population structure was highly correlated with gut environmental changes, including the accumulation of metabolites normally consumed by commensal microbiota. Finally, the less characterized phase of S. Typhimurium's lifecycle was investigated, and both proteomic and glycomic evidence suggests S. Typhimurium may take advantage of increased fucose moieties to metabolize fucose while growing in the gut. The application of multiple omics measurements to Salmonella-induced intestinal inflammation provides insights into complex molecular strategies employed during pathogenesis between host, pathogen, and the microbiome.
| S-EPMC3694140 | biostudies-literature
Project description:We report the dual RNA-sequencing of host and pathogen transcriptomes during Plasmodium berghei liver-stage development in vitro. Unlike traditional transcriptomic approaches that analyze RNA reads separately from host and pathogen, a dual-approach maps the mixed reads to each annotated genome within samples of pathogen-infected host cells. This is a powerful method, as host and pathogen transcriptomes can be analyzed simultaneously. We have taken advantage of this dual-RNA sequencing approach in order to gain insight into Plasmodium liver stage development within host hepatocytes. Huh7.5.1 hepatocytes were infected in vitro with P. berghei sporozoites freshly dissected from infected Anopheles stephansi mosquitos, and cells were collected throughout liver-stage development. This included samples collected at time zero (uninfected hepatocytes and sporozoites before infection), time 24 hours post infection (when the sporozoites have transformed into trophozoites), and time 48-50 hours post infection (when the trophozoites have transformed into liver-stage schizonts).
2018-03-06 | GSE78931 | GEO