Toxigenic C. difficile
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ABSTRACT:
PROVIDER: PRJEB65717 | ENA |
REPOSITORIES: ENA
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Project description:Culture of non-toxigenic Clostridioides difficile
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Project description:Gene expression level of Clostridioides difficile (C. difficile) strain R20291 comparing control C. difficile carring pMTL84151 as vector plasmid with C. difficile conjugated with a pMTL84151-03890 gene. Goal was to determine the effects of 03890 gene conjugation on C. difficile strain R20291 gene expression.
2023-11-30 | GSE219066 | GEO
Project description:The intestines house a diverse microbiota that must compete for nutrients to survive, but the specific limiting nutrients that control pathogen colonization are not clearly defined. Clostridioides difficile colonization typically requires prior disruption of the microbiota, suggesting that outcompeting commensals for resources is key in establishing C. difficile infection (CDI). The immune protein calprotectin (CP) is released into the gut lumen during CDI to chelate zinc (Zn) and other essential nutrient metals. Yet, the impact of Zn limitation on C. difficile colonization is unknown. To define C. difficile responses to Zn limitation, we performed RNA sequencing on C. difficile exposed to CP. In media with CP, C. difficile upregulated genes involved in metal homeostasis and amino acid metabolism.
2019-10-24 | GSE135912 | GEO
Project description:Clostridioides difficile interactions with the gut mucosa are crucial for colonisation and establishment of infection, however key infection events during the establishment of disease are still poorly defined. To better understand the initial events that occur during C. difficile colonisation, we employed a dual RNA-sequencing approach to study the host and bacterial transcriptomic profiles during C. difficile infection in a dual-environment in vitro human gut model. Temporal changes in gene expression were analysed over 3-24h post infection and comparisons were made with uninfected controls.
2023-03-23 | E-MTAB-12660 | biostudies-arrayexpress
Project description:Clostridioides difficile can cause severe infections in the gastrointestinal tract and affects almost half a million people in the U.S every year. Upon establishment of infection, a strong immune response is induced. We sought to investigate the dynamics of the mucosal host response during C. difficile infection.
2023-09-13 | GSE237574 | GEO
Project description:Clostridioides difficile is one of the most common nosocomial pathogens and a global public health threat. Upon colonization of the gastrointestinal tract, C. difficile is exposed to a rapidly changing polymicrobial environment and a dynamic metabolic milieu. Despite the link between the gut microbiota and susceptibility to C. difficile, the impact of synergistic interactions between the microbiota and pathogens on the outcome of infection is largely unknown. Here, we show that microbial cooperation between C. difficile and Enterococcus has a profound impact on the growth, metabolism, and pathogenesis of C. difficile.. Through a process of nutrient restriction and metabolite cross-feeding, E. faecalis shapes the metabolic environment in the gut to enhance C. difficile fitness and increase toxin production. These findings demonstrate that members of the microbiota, such as Enterococcus, have a previously unappreciated impact on C. difficile behavior and virulence.
2022-09-17 | GSE165751 | GEO
Project description:Unraveling Cecal Alterations in Clostridioides difficile Colonized Mice through a Comprehensive Metabolic Profile of 289 Compound
2024-07-10 | MSV000095285 | MassIVE
Project description:Defining the complex role of the microbiome in colorectal cancer (CRC) and the discovery of novel, pro-tumorigenic microbes are areas of active investigation. In the present study, culturing and reassociation experiments revealed that toxigenic strains of Clostridioides difficile drove the tumorigenic phenotype of a subset of CRC patient-derived mucosal slurries in germ-free ApcMin/+ mice. Tumorigenesis was dependent on the C. difficile toxin TcdB and was associated with induction of Wnt signaling, reactive oxygen species, and pro-tumorigenic mucosal immune responses marked by infiltration of activated myeloid cells and interleukin-17 (IL-17)-producing lymphoid and innate lymphoid cell subsets. In vitro, purified TcdB directly induced DNA strand breaks at low picomolar concentrations. These findings suggest that chronic colonization with toxigenic C. difficile is a potential driver of CRC in patients. Comparing scRNA-seq from mouse colon tissue 2 weeks after inoculation with different bacterial slurries
2022-05-27 | GSE200969 | GEO
Project description:Many enzymes require post-translational modifications or cofactor machinery for primary function. As these catalytically essential moieties are highly regulated, they act as dual sensors and chemical handles for context-dependent metabolic activity. Clostridioides difficile is a major nosocomial pathogen that infects the colon. Energy generating metabolism, particularly through amino acid Stickland fermentation, is central to colonization and persistence of this pathogen during infection. Here using activity-based protein profiling (ABPP), we revealed Stickland enzyme activity is a biomarker for C. difficile infection (CDI) and annotated two such cofactor-dependent Stickland reductases. We, for the first time, structurally assigned proline reductase and glycine reductase as cysteine-derived pyruvoyl-dependent enzymes and showed through cofactor monitoring that their activity is regulated by their respective amino acid substrates. Proline reductase was consistently active in toxigenic C. difficile, confirming the enzyme to be a major metabolic driver of CDI. Further, activity-based hydrazine probes were shown to be active site directed inhibitors of proline reductase. As such, this enzyme activity, via its druggable cofactor modality, is a promising therapeutic target that could allow for the repopulation of bacteria that compete with C. difficile for proline and therefore restore colonization resistance against C. difficile in the gut.
2023-03-11 | PXD039143 | Pride
Project description:Metabolomic and transcriptomic analysis of changes in the exponential and stationary phase of Clostridioides difficile after cultivation in casamino acids medium (reference) and supplemented with L-lactate and the connection to toxin production.
2021-01-31 | GSE139354 | GEO