Clostridioides difficile
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA338449 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4017800.fastq.gz | Fastqsanger.gz | |||
| SRR4017801.fastq.gz | Fastqsanger.gz | |||
| SRR4017802.fastq.gz | Fastqsanger.gz | |||
| SRR4017799.fastq.gz | Fastqsanger.gz |
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Project description:Clostridium difficile is an important nosocomial pathogen and the leading cause of hospital-acquired diarrhea. Antibiotic use is the primary risk factor for the development of C. difficile-associated disease because it disrupts normal protective gut flora and enables C. difficile to colonize the colon. C. difficile damages host tissue by secreting toxins and disseminates by forming spores. The toxin-encoding genes, tcdA and tcdB are part of a pathogenicity locus, which also encodes the gene tcdR that codes for the toxin genes positive regulator. TcdR is an alternate sigma factor that initiates transcription of tcdA and tcdB at their promoters. Alternative sigma factors are known to regulate virulence and virulence associated genes in many pathogenic bacteria. We created a tcdR mutant in the epidemic-type C. difficile R20291 strain in an attempt to identify the global role of tcdR. A site-directed mutation in tcdR affected both toxin production and sporulation in C. difficile R20291. Spores derived from the tcdR mutant were found to be mildly temperature sensitive. Moreover, nearly two fold more taurocholate was needed to germinate spores from the tcdR mutant than the spores prepared from the wild-type parent strain. Comparison of the tcdR mutant transcriptome with the parent strain revealed many differentially expressed late sporulation genes in the tcdR mutant. These data suggests that gene regulatory networks of toxin production and sporulation in Clostridium difficile are linked with each other.
2017-03-07 | GSE85395 | 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:Global analysis of genes induced during sporulation of Clostridium difficile
| PRJNA196825 | ENA
Project description:Purpose: A goal of this study was to identify genes induced in the mother cell during Clostridium difficile sporulation (specifically in a σE-, σK-, and SpoIIID-dependent manner). Methods: Whole genome RNA sequencing was performed on wildtype, sigE-, sigK- and spoIIID- C. difficile strains (strain 630 background; JIR8094 = parent strain), and the transcriptional profiles of the different mutants during growth on 70:30 agar plates were determined using an Illumina MiSeq1000. Results: This analysis identified 200 genes whose expression is collectively activated by sporulation sigma factors: 159 were σF-dependent, 162 were σE-dependent, 28 were σG-dependent, and 36 were σK-dependent. A total of 254 genes were identified as requiring Spo0A for their expression when sporulation was induced on the 70:30 plates. Conclusions: These results provide the first genome-wide transcriptional analysis of genes whose expression is induced by specific sporulation sigma factors in the Clostridia and highlight that diverse mechanisms regulate sporulation sigma factor activity in the Firmicutes. For example, in contrast with the B. subtilis sporulation pathway, C. difficile σE was not required to fully activate σG, and σG was not required to activate σK.
2014-12-02 | GSE63777 | GEO
Project description:Regulation of σK activity and function by SpoIIID during Clostridium difficile sporulation
| PRJNA269057 | ENA
Project description:CodY regulation of sporulation in Clostridioides difficile
| PRJNA1263881 | ENA
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: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 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