Synthetic bacterium
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1136646 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29857600_1.fastq.gz | Fastqsanger.gz | |||
| SRR29857600_2.fastq.gz | Fastqsanger.gz | |||
| SRR29857700_1.fastq.gz | Fastqsanger.gz | |||
| SRR29857700_2.fastq.gz | Fastqsanger.gz | |||
| SRR29857800_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 1046 |
Similar Datasets
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:The gut microbiome engenders colonization resistance against the diarrheal pathogen Clostridioides difficile but the molecular basis of this colonization resistance is incompletely understood. A prominent class of gut microbiome-produced metabolites important for colonization resistance against C. difficile is short chain fatty acids (SCFAs). In particular, one SCFA (butyrate) decreases the fitness of C. difficile in vitro and is correlated with C. difficile-inhospitable gut environments, both in mice and in humans. Here, we demonstrate that butyrate-dependent growth inhibition in C. difficile occurs under conditions where C. difficile also produces butyrate as a metabolic end product. Furthermore, we show that exogenous butyrate is internalized into C. difficile cells and is incorporated into intracellular CoA pools where it is metabolized in a reverse (energetically unfavorable) direction to crotonyl-CoA and (S)-3-hydroxybutyryl-CoA and/or 4-hydroxybutyryl-CoA. This internalization of butyrate and reverse metabolic flow of butyrogenic pathway(s) in C. difficile coincides with alterations in toxin release and sporulation. Together, this work highlights butyrate as a marker of a C. difficile inhospitable environment to which C. difficile responds by releasing its diarrheagenic toxins and producing environmentally-resistant spores necessary for transmission between hosts. These findings provide foundational data for understanding the molecular and genetic basis of how C. difficile growth is inhibited by butyrate and how butyrate alters C. difficile virulence in the face of a highly competitive and dynamic gut environment.
2023-12-21 | GSE249810 | GEO
Project description:We illustrate how metabolically distinct species of Clostridia can protect against or worsen Clostridioides difficile infection, modulating the pathogen's colonization, growth, and virulence to impact host survival. Gnotobiotic mice colonized with the amino acid fermenter Paraclostridium bifermentans survived infection while mice colonized with the butyrate-producer, Clostridium sardiniense, more rapidly succumbed. Systematic in vivo analyses revealed how each commensal altered the gut nutrient environment, modulating the pathogen's metabolism, regulatory networks, and toxin production. Oral administration of P. bifermentans rescued conventional mice from lethal C. difficile infection via mechanisms identified in specifically colonized mice. Our findings lay the foundation for mechanistically informed therapies to counter C. difficile disease using systems biologic approaches to define host-commensal-pathogen interactions in vivo.
2021-10-04 | GSE182613 | 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:The anaerobic, spore-forming pathogen Clostridioides difficile infects the gastrointestinal tract of higher mammals, including humans, and is the major causative agent of antibiotic-associated diarrhea. Moreover, recurrence and re-infection rates after a first successful antibiotic therapy are substantially high. To overcome the problem of recurrence and re-infection new antibiotics are urgently required that are more selective for the pathogen but spare other members of the microbiota. In turn, the microbial community inside the intestine is allowed to recover and to re-establish colonization resistance to protect against recurrence. The data presented here aim at analyzing the ability of the macrolide compound chlorotonil A to meet the requirements of C. difficile specific drug.
2023-03-29 | PXD029243 | Pride
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: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:Unraveling Cecal Alterations in Clostridioides difficile Colonized Mice through a Comprehensive Metabolic Profile of 289 Compound
2024-07-10 | MSV000095285 | MassIVE
Project description:The pathogen Clostridioides difficile causes toxin-mediated diarrhea and is the leading cause of hospital-acquired infection in the United States. Due to growing antibiotic resistance and recurrent infection, targeting C. difficile metabolism presents a new approach to combat this infection. Genome-scale metabolic network reconstructions (GENREs) have been used to identify therapeutic targets and uncover properties that determine cellular behaviors. Thus, we constructed C. difficile GENREs for a hypervirulent isolate (strain [str.] R20291) and a historic strain (str. 630), validating both with in vitro and in vivo data sets. Growth simulations revealed significant correlations with measured carbon source usage (positive predictive value [PPV] ≥ 92.7%), and single-gene deletion analysis showed >89.0% accuracy. Next, we utilized each GENRE to identify metabolic drivers of both sporulation and biofilm formation. Through contextualization of each model using transcriptomes generated from in vitro and infection conditions, we discovered reliance on the pentose phosphate pathway as well as increased usage of cytidine and N-acetylneuraminate when virulence expression is reduced, which was subsequently supported experimentally. Our results highlight the ability of GENREs to identify novel metabolite signals in higher-order phenotypes like bacterial pathogenesis.
2023-11-27 | MODEL2205060002 | BioModels
Project description:Clostridioides difficile (formerly Clostridium difficile) is a Gram-positive, spore-forming pathogen which cases drug-induced Clostridioides difficile-associated diseases in hospitals worldwide. A detailed analysis of the proteome may provide new targets for drug development or therapy strategies to combat this pathogen. So far, quantitative proteome analyses could only be carried out by label-free or chemical labeling methods. However, the application of metabolic labeling would allow for accurate quantification of significant differences, even in the case of very small changes. Additionally, it would be possible to perform bias free studies of the membrane or surface proteome which require elaborated preparations and are therefore prone to higher standard deviations during the quantification. Up to now, the implementation of metabolic labeling strategies of C. difficile was hampered by the very specific metabolic requirements of this anaerobic pathogen. To solve this problem, media were evaluated and the cultivation procedure with 15N labeled media for the C. difficile 630Δerm strain was optimized to gain a high incorporation rate. In the following proof-of-principle experiment, the cytosolic sub-proteomes of C. difficile cells of three different cultivation media and two growth phases were analyzed resulting in reproducible data which are shown in detail.
2018-10-25 | PXD010279 | Pride