Difficile

UNLABELLED: Paeniclostridium sordellii hemorrhagic toxin (TcsH) and Clostridioides difficile toxin A (TcdA) are two major members of the large clostridial toxin (LCT) family. These two toxins share ~87% similarity and are known to cause severe hemorrhagic pathology in animals. Yet, the pathogenesis of their hemorrhagic toxicity has been mysterious for decades. Here, we examined the liver injury after systemic exposure to different LCTs and found that only TcsH and TcdA induce overt hepatic hemorrhage...

Clostridioides difficile infection (CDI) with high morbidity and high mortality is an urgent threat to public health, and C. difficile pathogenesis studies are eagerly required for CDI therapy. The major surface layer protein, SlpA, was supposed to play a key role in C. difficile pathogenesis; however, a lack of isogenic slpA mutants has greatly hampered analysis of SlpA functions. In this study, the whole slpA gene was successfully deleted for the first time via CRISPR-Cas9 system. Deletion of slpA in C. difficile resulted in smaller, smother-edged colonies, shorter bacterial cell size, and aggregation in suspension...

INTRODUCTION: Practising medicine exposes physicians to emotionally difficult situations, which can be devastating, and for which they might be unprepared. Informal peer support has been recognised as helpful, although this phenomenon is understudied. Hence, it is important to develop a better understanding of the features of helpful informal peer support from the experiences of physicians who have successfully moved through such difficult events. This could lead to new and potentially more effective ways to support struggling physicians...

BACKGROUND: Clostridioides difficile is a leading cause of infectious diarrhea in both humans and livestock. In particular, C. difficile strains belonging to sequence type (ST) 11 are common enteropathogens. The aim of this study was to determine the presence and genetic relatedness of C. difficile types in dairy cattle and calves. METHOD: Dutch dairy farms were visited between February and December 2021. Feces was collected from adult dairy cattle and calves of two age categories (<4 weeks and 4 weeks-4 months)...

OBJECTIVE: To describe an outbreak of sequence type (ST)2 Clostridioides difficile infection (CDI) detected by a recently implemented multilocus sequence type (MLST)-based prospective genomic surveillance system using Oxford Nanopore Technologies (ONT) sequencing. SETTING: Hemato-oncology ward of a public tertiary referral centre. METHODS: From February 2022, we began prospectively sequencing all C. difficile isolated from inpatients at our institution on the ONT MinION device, with the output being an MLST...

The role of the healthcare environment in the transmission of clinical pathogens is well established. We investigated the chemical stability and sporicidal efficacy of oxidising disinfectant products in the presence of simulated clean and medical dirty conditions. Performance of chlorine-releasing agents (sodium dichloroisocyanurate, chlorine dioxide and hypochlorous acid) was concentration-dependent, with 1000 ppm chlorine showing reduced stability and efficacy in dirty conditions. In contrast peracetic acid product demonstrated stability and consistently achieved efficacy in dirty conditions...

Mono-O-glycosylation of target proteins by bacterial toxins or effector proteins is a well-known mechanism by which bacteria interfere with essential functions of host cells. The respective glycosyltransferases are important virulence factors such as the Clostridioides difficile toxins A and B. Here, we describe two glycosyltransferases of Yersinia species that have a high sequence identity: YeGT from the zoonotic pathogen Yersinia enterocolitica and YkGT from the murine pathogen Yersinia kristensenii. We show that both modify Rho family proteins by attachment of N-acetylglucosamine (GlcNAc) at tyrosine residues (Tyr-34 in RhoA)...

BACKGROUND: Clostridioides difficile infection (CDI) causes a major burden to individuals and society, yet the impact may vary depending on age, sex, underlying comorbidities and where CDI was acquired (hospital or community). METHODS: This Swedish nationwide population-based cohort study (2006-2019) compared all 43,150 individuals with CDI to their 355,172 matched controls (first year and entire follow-up). Negative binomial regression models compared the cumulated length of stay, number of in-hospital admissions, outpatient visits and prescriptions after the first CDI episode expressed as incidence rate ratios (IRR) and 95% confidence intervals for the entire follow-up...

OBJECTIVES: Clostridioides difficile infection (CDI) is the leading hospital-acquired infection in North America. We have previously discovered that antibiotic disruption of the gut microbiota decreases intestinal IL-33 and IL-25 and increases susceptibility to CDI. We further found that IL-33 promotes protection through type 2 Innate Lymphoid Cells (ILC2s), which produce IL-13. However, the contribution of IL-13 to disease has never been explored. METHODS: We used a validated model of CDI in mice, in which we neutralized via blocking antibodies, or administered recombinant protein, IL-13 to assess the role of this cytokine during infection using weight and clinical scores...

Clostridioides difficile infection causes pathology that ranges in severity from diarrhea to pseudomembranous colitis. Toxin A and Toxin B are the two primary virulence factors secreted by C. difficile that drive disease severity. The toxins damage intestinal epithelial cells leading to a loss of barrier integrity and induction of a proinflammatory host response. Monoclonal antibodies (mAbs) that neutralize Toxin A and Toxin B, actoxumab and bezlotoxumab, respectively, significantly reduce disease severity in a murine model of C...

Background Clostridioides difficile infection (CDI) represents a significant healthcare challenge associated with antibiotic use and healthcare settings. While healthcare facility-onset CDI (HO-CDI) rates have been extensively studied, the incidence and risk factors of CDI in various settings, including the community, require further investigation. Aim This study aims to examine the incidence rates of CDI in a major governmental hospital in Bahrain, identify risk factors for CDI, and assess the effectiveness of infection control measures...

OBJECTIVE: Data evaluating timeliness of antibiotic therapy in Clostridioides difficile infections (CDI) are not well established. The study's purpose was to evaluate the impact of time-to-CDI treatment on disease progression. METHODS: A case-control study was performed among hospitalized patients with CDI from 1/2018 to 2/2022. Inclusion criteria were age ≥65 years, first occurrence, non-severe CDI at symptom onset, and CDI treatment for ≥72 hours...

BACKGROUND: Many factors have been associated with the risk of toxigenic C. difficile diarrhea (TCdD). This study derived and internally validated a multivariate model for estimating the risk of TCdD in patients with diarrhea using readily available clinical factors. METHODS: A random sample of 3,050 symptomatic emergency department or hospitalized patients undergoing testing for toxigenic C. difficile at a single teaching hospital between 2014 and 2018 was created...

AIM: Our antimicrobial guidelines (AGs) were changed in 2021 to recommend once-daily ceftriaxone in place of three-times-daily cefuroxime as preferred cephalosporin. This analysis sought to assess the effects of this on incidence of Clostridioides difficile infection (CDI), third-generation cephalosporin-resistant Enterobacterales (3GCR-E) and resource utilisation. METHOD: Before and after analysis of 30-day CDI and 3GCR-E incidence following receipt of cefuroxime/ceftriaxone pre- and post-AG change...

BACKGROUND/AIM: Probiotics are live microbial supplements that improve the microbial balance in the host animal when administered in adequate amounts. They play an important role in relieving symptoms of many diseases associated with gastrointestinal tract, for example, in necrotizing enterocolitis (NEC), antibiotic-associated diarrhea, relapsing Clostridium difficile colitis, Helicobacter pylori infections, and inflammatory bowel disease (IBD). In this narrative review, the authors aim to evaluate the role of different probiotic formulations in treating gastrointestinal diseases in pediatric population aged 18 years or younger and highlight the main considerations for selecting probiotic formulations for use in this population...

Historically, mutagenesis in the non-model enteropathogenic bacterium Clostridioides difficile has been challenging. Developing a versatile and reliable method of generating targeted mutations in C. difficile is important to further our understanding of its pathogenesis. Some of the most common targeted mutagenesis systems rely on allelic exchange mediated by either uracil auxotrophy combined with a toxic uracil precursor, a toxin / anti-toxin system, group II introns, or CRISPR/Cas mutagenesis. However, each of these methods suffers from its own issues...

The dipeptide D-Ala-D-Ala is an essential component of peptidoglycan and the target of vancomycin. Most Clostridioides difficile strains possess the vanG operon responsible for the synthesis of D-Ala-D-Ser, which can replace D-Ala-D-Ala in peptidoglycan. The C. difficile vanG operon is regulated by a two-component system, VanRS, but is not induced sufficiently by vancomycin to confer resistance to this antibiotic. Surprisingly, in the absence of the VanS histidine kinase (HK), the vanG operon is still induced by vancomycin and also by another antibiotic, ramoplanin, in a VanR-dependent manner...

In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology . We focus specifically on the mechanisms un-derlying the effects of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), the factors which affect the outcomes of FMT in IBS patients, and challenges. FMT has emerged as a efficacious intervention for clostridium difficile infection and holds promise as a therapeutic modality for IBS. The utilization of FMT in the treatment of IBS has undergone scrutiny in numerous randomized controlled trials, yielding divergent outcomes...

OBJECTIVES: It has been estimated that vaccines can accrue a relatively large part of their value from patient and carer productivity. Yet, productivity value is not commonly or consistently considered in health economic evaluations of vaccines in several high-income countries. To contribute to a better understanding of the potential impact of including productivity value on the expected cost-effectiveness of vaccination, we illustrate the extent to which the incremental costs would change with and without productivity value incorporated...

Clostridioides difficile endolysin (Ecd09610) consists of an unknown domain at its N terminus, followed by two catalytic domains, a glucosaminidase domain and endopeptidase domain. X-ray structure and mutagenesis analyses of the Ecd09610 catalytic domain with glucosaminidase activity (Ecd09610CD53) were performed. Ecd09610CD53 was found to possess an α-bundle-like structure with nine helices, which is well conserved among GH73 family enzymes. The mutagenesis analysis based on X-ray structures showed that Glu405 and Asn470 were essential for enzymatic activity...