Network analysis of toxin production in Clostridioides difficile identifies key metabolic dependencies - PubMed
Clostridioides difficile pathogenesis is mediated through its two toxin proteins, TcdA and TcdB, which induce intestinal epithelial cell death and inflammation. It is possible to alter C. difficile toxin production by changing various metabolite concentrations within the extracellular environment. H …
In Vitro Selection and Characterization of a DNAzyme Probe for Diverse Pathogenic Strains of Clostridium difficile - PubMed
Clostridium difficile frequently causes an infectious disease known as Clostridium difficile infection (CDI) and there are urgent needs for the development of more effective rapid diagnostic tests for CDI. Previously we have developed an RNA-cleaving fluorogenic DNAzyme (RFD) probe named RFD-CD1, wh …
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...
Comparative Study of Adenosine Analogs as Inhibitors of Protein Arginine Methyltransferases and a Clostridioides difficile- Specific DNA Adenine Methyltransferase - PubMed
S-Adenosyl-l-methionine (SAM) analogs are adaptable tools for studying and therapeutically inhibiting SAM-dependent methyltransferases (MTases). Some MTases play significant roles in host-pathogen interactions, one of which is Clostridioides difficile-specific DNA adenine MTase (CamA). …
Comparative Study of Adenosine Analogs as Inhibitors of Protein Arginine Methyltransferases and a Clostridioides difficile- Specific DNA Adenine Methyltransferase - PubMed
S-Adenosyl-l-methionine (SAM) analogs are adaptable tools for studying and therapeutically inhibiting SAM-dependent methyltransferases (MTases). Some MTases play significant roles in host-pathogen interactions, one of which is Clostridioides difficile-specific DNA adenine MTase (CamA). …
Clinical Manifestations of Micronutrient Deficiencies in Short Bowel Syndrome: A Case Report
The etiologies of short bowel syndrome (SBS) can be stratified into congenital or acquired etiologies, with the latter being more prevalent. Small intestinal surgical resection is the most commo...
Practical observations on the use of fluorescent reporter systems in Clostridioides difficile - PubMed
Fluorescence microscopy is a valuable tool to study a broad variety of bacterial cell components and dynamics thereof. For Clostridioides difficile, the fluorescent proteins CFPsupopt/sup, mCherrysupOpt/sup and phiLOV2.1, and the self-labelling tags SNAPsupCd/sup and HaloTag, hereafter c …
On April 24th, @PeggyFund will host the 2023 National C. diff Advocacy Summit. During the event #CDiff patients, caregivers and healthcare industry members will discuss their experiences and strategies to fight this potentially life-threatening disease. https://t.co/WMnMENqxvp— MTIG (@MTIG_News) April 19, 2023
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.
