The evolution of antimicrobial resistance in Clostridioides difficile has markedly shaped its epidemiology and detrimentally impacted patient care. C. difficile exhibits resistance to multiple classes of antimicrobials, due to accumulation of horizontally acquired resistance genes and de novo mutati …

We isolated a rare strain of C. difficile producing only toxin B and lacking a complete tcdA gene herein Japan. The possibility of a false negative needs to be considered with a genetic method for a diagnose of C. difficile infection.

The switch from commensal to pathogenic is considered to be an important switch that has direct consequences on human health.

Gut microbiota composition during the first years of life is variable, dynamic and influenced by both prenatal and postnatal factors, such as maternal antibiotics administered during labor, delivery mode, maternal diet, breastfeeding, and/or antibiotic consumption during infancy. Furthermore, the mi …

The type A glycan modification found in human pathogen Clostridioides difficile consists of a monosaccharide (GlcNAc) that is linked to an N-methylated threonine through a phosphodiester bond. This structure has previously been described on the flagellar protein flagellin C of several C. difficile s …

The patient has been healthy for two months now after receiving the transplant in November.

Clostridium difficile is the principal cause of nosocomial infectious diarrhea worldwide. The pathogen modifies its flagellin with either a type A or type B O-linked glycosylation system, which has a contributory role in pathogenesis. We study the functional role of glycosyltransferases modifying ty …

Background: The human gut microbiota are important to health and wellness, and disrupted microbiota homeostasis, or "dysbiosis," can cause or contribute to many gastrointestinal disease states. Dysbiosis can be caused by many factors, most notably antibiotic treatment. To correct dysbiosis an …

Background: Clinicians need to better understand the value of computed tomography (CT) imaging and nonsurgical treatment options to manage acute left-sided colonic diverticulitis. Purpose: To evaluate CT imaging, outpatient treatment of uncomplicated diverticulitis, antibiotic treatment, and interventional radiology for patients with complicated diverticulitis. Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, CINAHL, and ClinicalTrials.gov from 1 January 1990 through 16 November 2020. Study Selection: Existing systematic reviews of CT imaging accuracy, as well as randomized trials and adjusted nonrandomized comparative studies reporting clinical or patient-centered outcomes. Data Extraction: 6 researchers extracted study data and risk of bias, which were verified by an independent researcher. The team assessed strength of evidence across studies. Data Synthesis: Based on moderate-strength evidence, CT imaging is highly accurate for diagnosing acute diverticulitis. For patients with uncomplicated acute diverticulitis, 6 studies provide low-strength evidence that initial outpatient and inpatient management have similar risks for recurrence or elective surgery, but they provide insufficient evidence regarding other outcomes. Also, for patients with uncomplicated acute diverticulitis, 5 studies comparing antibiotics versus no antibiotics provide low-strength evidence that does not support differences in risks for treatment failure, elective surgery, recurrence, posttreatment complications, and other outcomes. Evidence is insufficient to determine choice of antibiotic regimen (7 studies) or effect of percutaneous drainage (2 studies). Limitations: The evidence base is mostly of low strength. Studies did not adequately assess heterogeneity of treatment effect. Conclusion: Computed tomography imaging is accurate for diagnosing acute diverticulitis. For patients with uncomplicated diverticulitis, no differences in outcomes were found between outpatient and inpatient care. Avoidance of antibiotics for uncomplicated acute diverticulitis may be safe for most patients. The evidence is too sparse for other evaluated questions. Primary Funding Source: Agency for Healthcare Research and Quality and American College of Physicians. (PROSPERO: CRD42020151246)

Fidaxomicin (Fdx) is widely used to treat Clostridioides difficile ( Cdiff ) infections (CDIs), but the molecular basis of its narrow-spectrum activity in the human gut microbiome remains enigmatic. CDIs are a leading cause of nosocomial deaths. Fdx, which inhibits RNA polymerase (RNAP), targets Cdiff with minimal effects on gut commensals, reducing CDI recurrence. Here, we present the cryo-electron microscopy structure of Cdiff RNAP in complex with Fdx, allowing us to identify a crucial Fdx-binding determinant of Cdiff RNAP that is absent in most gut microbiota like Proteobacteria and Bacteroidetes. By combining structural, biochemical, and bioinformatic analyses, we establish that a single RNAP residue is a sensitizing element for Fdx narrow-spectrum activity. Our results provide a blueprint for targeted drug design against an important human pathogen. ### Competing Interest Statement The authors have declared no competing interest.

Patients with COVID-19 were not at an increased risk of developing CDI.

In conclusion: there is no ideal fluorescent system for #cdiff live cell imaging among those tested. The best system imho (#SNAP) still has the drawback of requiring a #substrate for fluorescence. 8/9— Wiep Klaas Smits (@SmitsLab) January 18, 2022

The last chapter of @AnaMOPaiva 's thesis is now published in @AvlJom; have a look for our observations on fluorescent #microscopy systems for #cdiff - short 🧵on our major findings https://t.co/mpjA1RvNls 1/9— Wiep Klaas Smits (@SmitsLab) January 18, 2022

Fluorescence microscopy is a valuable tool to study a broad variety of bacterial cell components and dynamics thereof. For Clostridioides difficile, the fluorescent proteins CFPopt, mCherryOpt and phiLOV2.1, and the self-labelling tags SNAPCd and HaloTag, hereafter c …

Clostridium difficile is an anaerobic, Gram-positive bacterium that is physiologically present in the bacterial flora of the vagina and...

A prototype biomarker that recognises antibiotic-induced gut dysbiosis has been created by a team from Ferring Pharmaceuticals, who believe the tool could help in developing future biotherapeutics.

The prototype is being tested in clinical trials involving live microbiota therapeutics as a treatment for recurrent C difficile infections.

#idtwitter Emergence of Clinical #Clostridioides difficile Isolates With Decreased Susceptibility to #Vancomycin https://t.co/2A9eR1ULaG @IDSAInfo Houston stool samples, 114/438 (26%) had vancomycin nonsusceptible #Cdiff isolates & 128/438 (29%) were metronidazole nonsusceptible— Saira Butt (@SAIRABT) January 9, 2022

The prototype is being tested in clinical trials involving live microbiota therapeutics as a treatment for recurrent C difficile infections.

Historically, methicillin-resistant Staphylococcus aureus (MRSA) was thought to be the primary pathogen in pseudomembranous enterocolitis associated with antibiotic use or recent abdominal surgery; however, Clostridioides difficile was later identified as another more common pathogen. Since t …

Clostridioides difficile infection is widespread throughout countries and represents an important cause of nosocomial diarrhoea, with relatively high morbidity. This infection often occurs in patients with inflammatory bowel diseases and may complicate their clinical picture. Here, we propose …

Antibiotics are only part of the problem.

Colitis is an inflammation of the lining of the colon that can cause pain and discomfort. Learn more about the types, common symptoms and treatments available.

The enteric pathogen Clostridioides difficile (Cd) is responsible for a toxin-mediated infection that causes more than 200,000 recorded hospitalizations and 13,000 deaths in the United States every year1. However, Cd can colonize the gut in the absence of disease symptoms. Prevalence of a …

Clostridioides difficile is the major cause of antibiotic-associated colitis (CDAC) with increasing prevalence in morbidity and mortality. Severity of CDAC has been attributed to hypervirulent C. difficile strains, which in addition to toxin A and B (TcdA, TcdB) produce the binary toxi …

Toxin A-negative, toxin B-positive Clostridioides difficile strains, which primarily include the ST81 and ST37 genotypes, are predominant in C. difficile infections leading to antibiotic-associated diarrhea in China. Recently, ST81 has been reported as the most prevalent genotype rathe …

Clostridioides difficile is often resistant to the actions of antibiotics to treat other bacterial infections and the resulting C. difficile infection (CDI) is among the leading causes of nosocomial infectious diarrhea worldwide. The primary virulence mechanism contributing to CDI is t …

In this paper, we present a comprehensive analysis of protein phosphorylation in the Gram-positive enteropathogen Clostridioides difficile. To date, only limited evidence on the role of phosphorylation in the regulation of this organism has been published;...

β-Lactam antibiotics, particularly cephalosporins, are major risk factors for C. difficile infection (CDI), the most common hospital acquired infection. These broad-spectrum antibiotics irreversibly inhibit penicillin-binding proteins (PBPs), essential enzymes that assemble the bacterial cell wall. Little is known about the C. difficile PBPs, yet they play central roles in the growth, infection, and transmission of this pathogen. In this study we discover that PBP2, essential for vegetative growth, is the primary bactericidal target for β-lactams in C. difficile. We further demonstrate PBP2 is insensitive to cephalosporin inhibition, revealing a key cause of the well-documented, but poorly understood, cephalosporin resistance in C. difficile. For the first time, we determine the crystal structures of C. difficile PBP2, which bears several highly unique features, including significant ligand-induced conformational changes and an active site Zn2+-binding motif that influences β-lactam binding and protein stability. Remarkably, this motif is shared in two other C. difficile PBPs essential for sporulation, PBP3 and SpoVD. While these PBPs are present in a wide range of bacterial taxa, including species in extreme environments and the human gut, they are mostly found in anaerobes, typically Firmicutes. The widespread presence of this convergently evolved thiol-containing motif and its cognate Zn2+ suggests it may function as a redox-sensor to regulate cell wall synthesis for survival in adverse environments. Collectively, our findings address important etiological questions surrounding C. difficile, characterize new elements of PBP structure and function, and lay the groundwork for antibiotic development targeting both C. difficile growth and sporulation. ### Competing Interest Statement The authors have declared no competing interest.