Synthesis of Muramyl-δ-Lactam in Spore Peptidoglycan of Clostridioides difficile - PubMed
Clostridioides difficile is a spore-forming human pathogen responsible for significant morbidity and mortality. Infections by this pathogen ensue dysbiosis of the intestinal tract, which lead to germination of the spores. The process of spore formation requires a transition for the cell-wall peptido …
Synthesis of Muramyl-δ-Lactam in Spore Peptidoglycan of Clostridioides difficile - PubMed
Clostridioides difficile is a spore-forming human pathogen responsible for significant morbidity and mortality. Infections by this pathogen ensue dysbiosis of the intestinal tract, which lead to germination of the spores. The process of spore formation requires a transition for the cell-wall peptido …
Targeting the human gut microbiome with small-molecule inhibitors
Nature Reviews Chemistry - Small-molecule inhibitors offer many advantages for manipulating the gut microbiome, both as tool compounds and as potential therapeutics. This Review highlights recent...
Draft Genome Sequences and Genome Characterization of Three Toxigenic and Two Nontoxigenic Clostridioides difficile Clinical Isolates from Florida, USA - PubMed
Draft genome sequences of five Clostridioides difficile clinical isolates were obtained in Florida, USA. Three isolates, designated TGH29 (sequence type 1 [ST1]/clade 2), TGH79 (ST11/clade 5), and TGH91 (ST35/clade 1), contained toxin-encoding genes. The two nontoxigenic strains were classified as T …
Clostridioides difficile minimal nutrient requirements for flagellar motility - PubMed
As many gastro-intestinal pathogens, the majority of Clostridioides difficile strains express flagella together with a complete chemotaxis system. The resulting swimming motility is likely contributing to the colonization success of this important pathogen. In contrast to the well investigate …
Clostridium difficile Infection Is Associated With Decreased Prostate Cancer Risk: A Retrospective Cohort Study
Background Clostridium difficile (C. difficile) is one of the most common hospital-acquired infections and causes the release of various cytokines. Prostate cancer (PC) is the second most com...
The ‘Whey’ to good health: Whey protein and its beneficial effect on metabolism, gut microbiota and mental health
Whey protein (WP) and its components account for 20% of bovine milk proteins. Once considered as a waste by-product of cheese production, WP is now kn…
A Cross-Sectional Study of Clostridium Difficile Infection in Inpatients with Antibiotic Associated Diarrhea - PubMed
The incidence of CDI in the southern area of China was low. Age 60 years, and treatment in geriatric or neurosurgery units were independent risk factors for CDI inpatients.
A leaky human colon model reveals uncoupled apical/basal cytotoxicity in early Clostridioides difficile toxin exposure | American Journal of Physiology-Gastrointestinal and Liver Physiology
Clostridioides difficile (C. difficile) toxins A (TcdA) and B (TcdB) cause antibiotic-associated colitis in part by disrupting epithelial barrier function. Accurate in vitro models are necessary to detect early toxicity kinetics, investigate disease etiology, and develop preclinical models for new therapies. Properties of cancer cell lines and organoids inherently limit these efforts. We developed adult stem cell-derived monolayers of differentiated human colonic epithelium (hCE) with barrier function, investigated the impact of toxins on apical/basal aspects of monolayers, and evaluated whether a leaky epithelial barrier enhances toxicity. Single-cell RNA-sequencing (scRNAseq) mapped C. difficile-relevant genes to human lineages. Transcriptomics compared hCE to Caco-2, informed timing of in vitro stem cell differentiation, and revealed transcriptional responses to TcdA. Transepithelial electrical resistance (TEER) and fluorescent permeability assays measured cytotoxicity. Contribution of TcdB toxicity was evaluated in a diclofenac-induced leaky gut model. scRNAseq demonstrated broad and variable toxin receptor expression. Absorptive colonocytes in vivo displayed increased toxin receptor, Rho GTPase, and cell junction gene expression. Advanced TcdA toxicity generally decreased cytokine/chemokine and increased tight junction and death receptor genes. Differentiated Caco-2 cells remained immature whereas hCE monolayers were similar to mature colonocytes in vivo. Basal exposure of TcdA/B caused greater toxicity and apoptosis than apical exposure. Apical exposure to toxins was enhanced by diclofenac. Apical/basal toxicities are uncoupled with more rapid onset and increased magnitude postbasal toxin exposure. Leaky junctions enhance toxicity of apical TcdB exposure. hCE monolayers represent a physiologically relevant and sensitive system to evaluate the impact of microbial toxins on gut epithelium. NEW & NOTEWORTHY Novel human colonocyte monolayer cultures, benchmarked by transcriptomics for physiological relevance, detect early cytopathic impacts of Clostridioides difficile toxins TcdA and TcdB. A fluorescent ZO-1 reporter in primary human colonocytes is used to track epithelial barrier disruption in response to TcdA. Basal TcdA/B exposure generally caused more rapid onset and cytotoxicity than apical exposure. Transcriptomics demonstrate changes in tight junction, chemokine, and cytokine receptor gene expression post-TcdA exposure. Diclofenac-induced leaky epithelium enhanced apical exposure toxicity.
Gene network interaction analysis to elucidate the antimicrobial resistance mechanisms in the Clostridiumdifficile - PubMed
Antimicrobial resistance has caused chaos worldwide due to the depiction of multidrug-resistant (MDR) infective microorganisms. A thorough examination of antimicrobial resistance (AMR) genes and associated resistant mechanisms is vital to solving this problem. Clostridium difficile (C. difficile) is …
A Conserved Switch Controls Virulence, Sporulation, and Motility in C. difficile - PubMed
Spore formation is required for environmental survival and transmission of the human enteropathogenic Clostridioides difficile . In all bacterial spore formers, sporulation is regulated through activation of the master response regulator, Spo0A. However, the factors and mechanisms that direct …
Mortality Rate Higher in Colorectal Cancer Patients Diagnosed Without a Colonoscopy
Patients with no prior colonoscopy had significantly higher all-cause mortality and colorectal cancer specific mortality compared to patients with detected colorectal cancer.
Scientists succeeded in defining a new algorithm to systematically profile gut microbiome metabolism, identifying 19,890 gene clusters in 4,240 high-quality microbial genomes:https://t.co/c7GNu7mtiZ— GutMicrobiota Health (@GMFHx) April 7, 2023
Mechanism of germination inhibition of Clostridioides difficile spores by an aniline substituted cholate derivative (CaPA) - PubMed
Clostridioides difficile infection (CDI) is the major identifiable cause of antibiotic-associated diarrhea and has been declared an urgent threat by the CDC. C. difficile forms dormant and resistant spores that serve as infectious vehicles for CDI. To cause disease, C. difficile spores recognize tau …
IBS Survey Shows High Levels of Uncertainty on Symptoms, Treatment
The majority of patients felt it was important for healthcare providers talk to them about the symptoms, possible treatments. In addition, most patients are not prescribed a medication right away.
Penicillin Binding Protein Substitutions Cooccur with Fluoroquinolone Resistance in Epidemic Lineages of Multidrug-Resistant Clostridioides difficile - PubMed
Clostridioides difficile remains a key cause of healthcare-associated infection, with multidrug-resistant (MDR) lineages causing high-mortality (≥20%) outbreaks. Cephalosporin treatment is a long-established risk factor, and antimicrobial stewardship is a key control. A mechanism underlying raised c …
Mechanism of germination inhibition of Clostridioides difficile spores by an aniline substituted cholate derivative (CaPA) - PubMed
Clostridioides difficile infection (CDI) is the major identifiable cause of antibiotic-associated diarrhea and has been declared an urgent threat by the CDC. C. difficile forms dormant and resistant spores that serve as infectious vehicles for CDI. To cause disease, C. difficile spores recognize tau …
Mechanism of germination inhibition of Clostridioides difficile spores by an aniline substituted cholate derivative (CaPA)
The Journal of Antibiotics - Mechanism of germination inhibition of Clostridioides difficile spores by an aniline substituted cholate derivative (CaPA)
#Cdiff is anaerobic, gram-positive bacterium that exists in both vegetative and spore forms. #GITwitter #IDTwitter #guthealth pic.twitter.com/dShF4xROao— Microbiome Science (@MbiomeScience) April 2, 2023
Checkpoint Inhibitor Colitis With Superimposed Clostridioides difficile Infection
Immune checkpoint inhibitors (ICI) are commonly used for various malignancies. A particular checkpoint inhibitor is the anti-PD-1 antibody pembrolizumab. Immune-mediated diarrhea and colitis (IM...
Dormant Crohn's Disease Reactivated by Clostridioides difficile Infection
Crohn’s disease (CD) is a type of inflammatory bowel disease (IBD) characterized by chronic transmural inflammation of any portion of the gastrointestinal tract. The etiology of CD remains unkno...
Checkpoint Inhibitor Colitis With Superimposed Clostridioides difficile Infection
Immune checkpoint inhibitors (ICI) are commonly used for various malignancies. A particular checkpoint inhibitor is the anti-PD-1 antibody pembrolizumab. Immune-mediated diarrhea and colitis (IM...
“Recent findings show infants born to mothers with IBD present with altered gut microbiome that transfers abnormalities of the adaptive immune system to germ-free mice.
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Genetic diversity of C. difficile, a particularly problematic pathogen
Researchers have used a systems biology approach to parse the genetic diversity of Clostridioides difficile, a particularly problematic pathogen, particularly in health care settings.
Teams identifies protein characteristics in three bacteria that convey antibiotic resistance
Antibiotic resistance (ARE) is a threat to human health worldwide, as diverse proteins allow pathogenic bacteria to develop increasing levels of resistance to antibiotic medicines. Now, a team from the ...
Non-Toxigenic Clostridioides difficile Strain E4 (NTCD-E4) Prevents Establishment of Primary C. difficile Infection by Epidemic PCR Ribotype 027 in an In Vitro Human Gut Model - PubMed
Clostridioides difficile infection (CDI) remains a significant healthcare burden. Non-toxigenic C. difficile (NTCD) strains have shown a benefit in preventing porcine enteritis and in human recurrent CDI. In this study, we evaluated the efficacy of metronidazole-resistant NTCD-E4 in pr …
