Dual RNA-seq of clinical adult sepsis samples (TOPS study) to characterize host-pathogen interactions
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PROVIDER: PRJEB83767 | ENA |
REPOSITORIES: ENA
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Project description:Blood samples (0.5 ml) of 8 adults with blood culture-confirmed bacterial sepsis and 3 healthy adults were collected. A previously optimized host-bacterial RNA extraction protocol was used to isolate leukocyte and bacterial RNA. Purified RNA was depleted or rRNA and underwent deep sequencing using a 150 bp paired-end sequencing run on a NovaSeq 6000 (Illumina). Host and bacterial sequencing reads were aligned in silico and bioinformatic analyses were used to explore host and bacterial transcriptional responses during sepsis.
2025-02-03 | E-MTAB-14713 | biostudies-arrayexpress
Project description:Cronobacter (C.) is an important emerging opportunistic foodborne pathogen representing significant cause of mortality in neonatal patients with bacteremia and meningitis. Knowledge on the pathobiology of Cronobacter mediated meningitis has to a large extend been explored using in vitro models. To explore the innate immune response against the neonatal sepsis/meningitis causing isolate C. turicensis z3032 in vivo, zebrafish larvae (Danio rerio) were used as infection model. Following establishment of infection in zebrafish larvae with z3032, dual RNA-sequencing of host-pathogen was undertaken to profile RNA expression simultaneously in the pathogen and the head region of the zebrafish host.
2025-10-31 | GSE236051 | GEO
Project description:Dual transcriptome analysis of the V. vulnificus-infected human cells; To understand toxin-stimulated host-pathogen interactions, we set up dual transcriptome sequencing experiments using the human epithelial (HT-29) or immune (differentiated THP-1; dTHP-1) cells infected with the sepsis-causing pathogen Vibrio vulnificus, either in wild-type or the MARTX toxin-deficient backgrounds.
2020-08-03 | GSE136540 | GEO
Project description:We report the use of a Dual RNA-Seq approach to investigate the interaction of grapevine with the Botryosphaeria dieback agent L. theobromae. The aim of this work was to (1) identify pathogenicity factors produced by L. theobromae, and (2) determine the V. vinifera defence response to the pathogen.
2022-03-29 | GSE129109 | GEO
Project description:Dual-species proteomics and targeted intervention of animal-pathogen interactions
2022-08-17 | PXD036121 |
Project description:Burkholderia pathogenicity relies on protein virulence factors to control and promote bacterial internalization, survival, and replication within eukaryotic host cells. We recently used yeast two-hybrid (Y2H) screening to identify a small set of novel Burkholderia proteins that were shown to attenuate disease progression in an aerosol infection animal model using the virulent Burkholderia mallei ATCC 23344 strain. Here, we performed an extended analysis of primarily nine B. mallei virulence factors and their interactions with human proteins to map out how the bacteria can influence and alter host processes and pathways. Specifically, we employed topological analyses to assess the connectivity patterns of targeted host proteins, identify modules of pathogen-interacting host proteins linked to processes promoting infectivity, and evaluate the effect of crosstalk among the identified host protein modules. Overall, our analysis showed that the targeted host proteins generally had a large number of interacting partners and interacted with other host proteins that were also targeted by B. mallei proteins. We also introduced a novel Host-Pathogen Interaction Alignment (HPIA) algorithm and used it to explore similarities between host-pathogen interactions of B. mallei, Yersinia pestis, and Salmonella enterica. We inferred putative roles of B. mallei proteins based on the roles of their aligned Y. pestis and S. enterica partners and showed that up to 73% of the predicted roles matched existing annotations. A key insight into Burkholderia pathogenicity derived from these analyses of Y2H host-pathogen interactions is the identification of eukaryotic-specific targeted cellular mechanisms, including the ubiquitination degradation system and the use of the focal adhesion pathway as a fulcrum for transmitting mechanical forces and regulatory signals. This provides the mechanisms to modulate and adapt the host-cell environment for the successful establishment of host infections and intracellular spread.
| S-EPMC4349708 | biostudies-literature
Project description:The transcriptome is a powerful proxy for the physiological state of a cell, healthy or diseased. As a result, transcriptome analysis has become a key tool in understanding the molecular changes that accompany bacterial infections of eukaryotic cells. Until recently, such transcriptomic studies have been technically limited to analyzing mRNA expression changes in either the bacterial pathogen or the infected eukaryotic host cell. However, the increasing sensitivity of high-throughput RNA sequencing now enables "dual RNA-seq" studies, simultaneously capturing all classes of coding and noncoding transcripts in both the pathogen and the host. In the five years since the concept of dual RNA-seq was introduced, the technique has been applied to a range of infection models. This has not only led to a better understanding of the physiological changes in pathogen and host during the course of an infection but has also revealed hidden molecular phenotypes of virulence-associated small noncoding RNAs that were not visible in standard infection assays. Here, we use the knowledge gained from these recent studies to suggest experimental and computational guidelines for the design of future dual RNA-seq studies. We conclude this review by discussing prospective applications of the technique.
| S-EPMC5313147 | biostudies-literature
Project description:Dual transcriptomics of host-pathogen interaction of neonatal sepsis/meningitis causing isolate Cronobacter turicensis z3032 with zebrafish larvae
| PRJNA988505 | ENA
Project description:BackgroundFrancisella tularensis is a select bio-threat agent and one of the most virulent intracellular pathogens known, requiring just a few organisms to establish an infection. Although several virulence factors are known, we lack an understanding of virulence factors that act through host-pathogen protein interactions to promote infection. To address these issues in the highly infectious F. tularensis subsp. tularensis Schu S4 strain, we deployed a combined in silico, in vitro, and in vivo analysis to identify virulence factors and their interactions with host proteins to characterize bacterial infection mechanisms.ResultsWe initially used comparative genomics and literature to identify and select a set of 49 putative and known virulence factors for analysis. Each protein was then subjected to proteome-scale yeast two-hybrid (Y2H) screens with human and murine cDNA libraries to identify potential host-pathogen protein-protein interactions. Based on the bacterial protein interaction profile with both hosts, we selected seven novel putative virulence factors for mutant construction and animal validation experiments. We were able to create five transposon insertion mutants and used them in an intranasal BALB/c mouse challenge model to establish 50 % lethal dose estimates. Three of these, ΔFTT0482c, ΔFTT1538c, and ΔFTT1597, showed attenuation in lethality and can thus be considered novel F. tularensis virulence factors. The analysis of the accompanying Y2H data identified intracellular protein trafficking between the early endosome to the late endosome as an important component in virulence attenuation for these virulence factors. Furthermore, we also used the Y2H data to investigate host protein binding of two known virulence factors, showing that direct protein binding was a component in the modulation of the inflammatory response via activation of mitogen-activated protein kinases and in the oxidative stress response.ConclusionsDirect interactions with specific host proteins and the ability to influence interactions among host proteins are important components for F. tularensis to avoid host-cell defense mechanisms and successfully establish an infection. Although direct host-pathogen protein-protein binding is only one aspect of Francisella virulence, it is a critical component in directly manipulating and interfering with cellular processes in the host cell.
| S-EPMC4696196 | biostudies-literature
Project description:Background: Sepsis involves aberrant immune responses to infection, but the exact nature of this immune dysfunction remains poorly defined. Bacterial endotoxins like lipopolysaccharide (LPS) are potent inducers of inflammation, which has been associated with the pathophysiology of sepsis, but repeated exposure can also induce a suppressive effect known as endotoxin tolerance or cellular reprogramming. It has been proposed that endotoxin tolerance might be associated with the immunosuppressive state that was primarily observed during late-stage sepsis. However, this relationship remains poorly characterised. Here we clarify the underlying mechanisms and timing of immune dysfunction in sepsis. Methods: We defined a gene expression signature characteristic of endotoxin tolerance. Gene-set test approaches were used to correlate this signature with early sepsis, both newly and retrospectively analysing microarrays from 593 patients in 11 cohorts. Then we recruited a unique cohort of possible sepsis patients at first clinical presentation in an independent blinded controlled observational study to determine whether this signature was associated with the development of confirmed sepsis and organ dysfunction. Findings: All sepsis patients presented an expression profile strongly associated with the endotoxin tolerance signature (p < 0.01; AUC 96.1%). Importantly, this signature further differentiated between suspected sepsis patients who did, or did not, go on to develop confirmed sepsis, and predicted the development of organ dysfunction. Interpretation: Our data support an updated model of sepsis pathogenesis in which endotoxin tolerance-mediated immune dysfunction (cellular reprogramming) is present throughout the clinical course of disease and related to disease severity. Thus endotoxin tolerance might offer new insights guiding the development of new therapies and diagnostics for early sepsis. For the RNA-Seq study reported here, 73 patients were recruited with deferred consent at the time of first examination in an emergency ward based on the opinion of physicians that there was a potential for the patient's condition to develop into sepsis. These were retrospectively divided into groups based on clinical features and compared to 11 non-urgent surgical controls.
2014-11-14 | E-GEOD-63311 | biostudies-arrayexpress