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:Acinetobacter spp from Sulbactam-Durlobactam Surveillance study 2016-2021
Project description:Background: Clostridioides difficile (C. difficile) is a global threat and has significant implications for individuals and health care systems. Little is known about host molecular mechanisms and transcriptional changes in peripheral immune cells. This is the first gene expression study in whole blood of patients with C. difficile infection. Methods: We took blood and stool samples from patients with toxigenic C. difficile infection (CDI), non-toxigenic C. difficile infection (GDH), inflammatory bowel disease (IBD), diarrhoea from other causes (DC) and healthy controls (HC). We performed transcriptome-wide RNA profiling on peripheral blood to identify diarrhoea common and CDI unique gene sets. Results: Diarrhoea groups upregulated innate immune responses with neutrophils at the epicentre. The common signature associated with diarrhoea was non-specific and shared by various other inflammatory conditions. CDI had a unique 45-gene set reflecting downregulation of humoral and T cell memory functions. Dysregulation of immunometabolic genes was also abundant and linked to immune cell fate during differentiation. Conclusions: Whole transcriptome analysis of white cells in blood from patients with toxigenic C. difficile infection showed that there is an impairment of adaptive immunity and immunometabolism.
Project description:Clostridium difficile is a gram-positive, spore-forming enteric anaerobe which can infect humans and a wide variety of animal species. Recently, the incidence and severity of human C. difficile infection has markedly increased. In this study, we evaluated the genomic content of 73 C. difficile strains isolated from humans, horses, cattle, and pigs by comparative genomic hybridization with microarrays containing coding sequences from C. difficile strains 630 and QCD-32g58. The sequenced genome of C. difficile strain 630 was used as a reference to define a candidate core genome of C. difficile and to explore correlations between host origins and genetic diversity. Approximately 16% of the genes in strain 630 were highly conserved among all strains, representing the core complement of functional genes defining C. difficile. Absent or divergent genes in the tested strains were distributed across the entire C. difficile 630 genome and across all the predicted functional categories. Interestingly, certain genes were conserved among strains from a specific host species, but divergent in isolates with other host origins. This information provides insight into the genomic changes which might contribute to host adaptation. Due to a high degree of divergence among C. difficile strains, a core gene list from this study offers the first step toward the construction of diagnostic arrays for C. difficile.
Project description:Clostridium difficile is a gram-positive, spore-forming enteric anaerobe which can infect humans and a wide variety of animal species. Recently, the incidence and severity of human C. difficile infection has markedly increased. In this study, we evaluated the genomic content of 73 C. difficile strains isolated from humans, horses, cattle, and pigs by comparative genomic hybridization with microarrays containing coding sequences from C. difficile strains 630 and QCD-32g58. The sequenced genome of C. difficile strain 630 was used as a reference to define a candidate core genome of C. difficile and to explore correlations between host origins and genetic diversity. Approximately 16% of the genes in strain 630 were highly conserved among all strains, representing the core complement of functional genes defining C. difficile. Absent or divergent genes in the tested strains were distributed across the entire C. difficile 630 genome and across all the predicted functional categories. Interestingly, certain genes were conserved among strains from a specific host species, but divergent in isolates with other host origins. This information provides insight into the genomic changes which might contribute to host adaptation. Due to a high degree of divergence among C. difficile strains, a core gene list from this study offers the first step toward the construction of diagnostic arrays for C. difficile.investigated by determining changes in transcript profiles when aerobic steady-state cultures were depleted of air.