Clostridioides difficile
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA555604 | ENA |
REPOSITORIES: ENA
Similar Datasets
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: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: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 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:University of Michigan Clostridium difficile infection isolates
| PRJNA673132 | ENA
Project description:Clostridium difficile Biofilm with and without deoxycholate at 48H
| PRJNA339928 | ENA
Project description:Clostridioides difficile is the leading cause of nosocomial diarrhea, afflicting approximately half a million people each year in the USA, burdening both individuals’ quality of life and the healthcare system. In the gastrointestinal (GI) tract, C. difficile must acquire essential nutrients to colonize, establish infection, and persists in a polymicrobial environment. C. difficile is a cysteine auxotroph and the GI tract contains low levels of cysteine, highlighting gaps in our understanding of how C. difficile acquires this amino acid during infection. One possible source of cysteine for C. difficile during infection is glutathione (GSH), tripeptide thiol in mammalian cells. Our data indicate that C. difficile encodes two redundant enzymes (GecA and GecB) that allow it to use GSH as a source of cysteine. Using murine models of C. difficile infection, we also show that C. difficile uses its toxins to increase available GSH in the GI tract during infection. Finally, we show that the ability to utilize GSH gives wild-type C. difficile a fitness advantage over a GSH-deficient mutant in vivo. These findings establish GSH metabolism as a novel strategy of nutrient acquisition that links C. difficile metabolism and virulence and highlight GSH metabolism as possibly impactful target for future therapeutic development.
2026-06-10 | GSE310543 | 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