C Diff Molecular

Clostridioides difficile is a Gram-positive anaerobe that can cause a spectrum of disorders that range in severity from mild diarrhoea to fulminant colitis and/or death. The bacterium produces up to three toxins, which are considered the major virulence factors in C. difficile infection. These toxin …

The enteric pathogen Clostridioides difficile overcomes barriers to colonization imposed by the microbiota and host immune response to induce disease. To navigate the dynamic gut environment, C. difficile must respond to dietary and host-mediated fluctuations in transition metal availability. Transi …

Pro-Pro-endopeptidases (PPEP, EC 3.4.24.89) are secreted, zinc metalloproteases that have the unusual capacity to cleave a peptide bond between two prolines, a bond that is generally less sensitive to proteolytic cleavage. Two well studied members of the family are PPEP-1 and PPEP-2, produced by …

Body mass index was associated with C. difficile infection in older pneumonia patients in Japan. Underweight was a risk factor, whereas overweight was a protective factor for C. difficile infection. Geriatr Gerontol Int 2021; ••: ••-••.

The human pathogen Clostridioides difficile colonises the gastrointestinal tract following antibiotic exposure, which causes perturbations in the beneficial microbiome. An unusual feature of C. difficile among the gut microbiota is its ability to produce high concentrations of the antimicrobial comp …

Clostridioides difficile is classified as an urgent antibiotic resistance threat by the Centers for Disease Control and Prevention (CDC). C. difficile infection (CDI) is mainly caused by the C. difficile exotoxin TcdB, which invades host cells via receptor-mediated endocytosis. However, many natural …

Small, diffusible second messenger molecules transmit information about extracellular conditions to intracellular machinery in order to influence transcription, translation, and metabolism. The enteropathogenic bacterium Clostridioides difficile coordinates its response to a dynamic and hostile envi …

The panel reflects on how disruption of the gut microbiome leads to the proliferation of Clostridioides difficile.

Among adults who develop CDI after SOT or HSCT, despite their immunosuppressed state, the percentage with clinical cure was high and the percentage with recurrence was low. Clinical cure and recurrence varied by type of initial treatment, and CMV viremia/disease was associated with an increased risk …

Clostridioides difficile causes nosocomial diarrhoea associated with antibiotic use and immunodeficiency. Although the number of paediatric C. difficile infections (CDIs) has increased worldwide, there are few studies on the molecular characterization of strains causing CDIs among chil …

Clostridioides difficile infections have emerged as the leading cause of healthcare-associated infectious diarrhea. Disease symptoms are mainly caused by the virulence factors, TcdA and TcdB, which are large homologous multidomain proteins. Here, we report a 2.8 Å resolution cryo-EM structure of nat …

Germination by Clostridioides difficile spores is an essential step in pathogenesis. Spores are metabolically dormant forms of bacteria that resist severe conditions. Work over the last 10 years has elucidated that C. difficile spores germinate thorough a novel pathway. This review summarizes our un …

November is C. Diff Awareness Month but what exactly is C. diff and why does it deserve a national awareness month?

Our results indicate that procalcitonin level can be a good candidate biomarker for assessing the CDI in IBD patients. Further studies are required to decipher whether procalcitonin can predict CDI therapy or its recurrence.

The ability of the anaerobic gastrointestinal pathogen, Clostridioides difficile , to survive outside the host relies on the formation of dormant endospores. Spore formation is contingent on the activation of a conserved transcription factor, Spo0A, by phosphorylation. Multiple kinases and phosphatases regulate Spo0A activity in other spore-forming organisms; however, these factors are not well conserved in C. difficile . Previously, we discovered that deletion of a conserved phosphotransfer protein, CD1492, increases sporulation, indicating that CD1492 inhibits C. difficile spore formation. In this study, we investigate the functions of additional conserved orphan phosphotransfer proteins, CD2492, CD1579, and CD1949 which are hypothesized to regulate Spo0A phosphorylation. Disruption of the conserved phosphotransfer protein, CD2492, also increased sporulation frequency, similarly to the CD1492 mutant, and in contrast to a previous study. A CD1492 CD2492 mutant phenocopied the sporulation and gene expression patterns of the single mutants, suggesting that these proteins function in the same genetic pathway to repress sporulation. Deletion of the conserved CD1579 phosphotransfer protein also variably increased sporulation frequency; however, knockdown of CD1949 expression did not influence sporulation. We provide evidence that CD1492, CD2492 and CD1579 function as phosphatases, as mutation of the conserved histidine residue for phosphate transfer abolished CD2492 function, and expression of the CD1492 or CD2492 histidine site-directed mutants or the wild-type CD1579 allele in a parent strain resulted in a dominant negative hypersporulation phenotype. Altogether, at least three phosphotransfer proteins, CD1492, CD2492 and CD1579 (herein, PtpA, PtpB and PtpC) repress C. difficile sporulation initiation by regulating activity of Spo0A. ### Competing Interest Statement The authors have declared no competing interest.

Experts focus on recurrent clostridium difficile infection to define risk factors and discuss impact on patient outcomes.

Opening their discussion on Clostridioides difficile, experts provide an overview on the gut microbiome and colonization resistance.

People who respond well to the recommended dietary therapy of restricting intake of fermentable carbs for irritable bowel syndrome, or IBS for short, have an abundance of particular types of bacteria ...

There was an increased prevalence of community-acquired CDI, with a prevalence almost equal to that of hospital-acquired. In addition, most of the participants were immunocompromised. The risk factors for CDI, such as antibiotics and PPI use, were also observed with high prevalence among positive pa …

Clostridioides difficile has become the most common healthcare-associated pathogen in the United States, leading the US Centers for Disease Control and Prevention (CDC) to classify C. difficile as an "urgent" public health threat that requires "urgent and aggressive action." This call to action has …

Children with Clostridioides difficile infection (CDI) can experience recurrent or severe disease. Recurrent CDI occurs in 20%-30% of children with an initial CDI episode. A careful clinical evaluation is important to distinguish recurrent CDI from other disorders that cause recurring gastrointestin …

Clostridioides difficile is a spore-forming, obligate anaerobe, and ubiquitous nosocomial pathogen. While C. difficile infection in adults causes a spectrum of disease, including pseudomembranous colitis and toxic megacolon, healthy infants are asymptomatically colonized at high rates. The mechanism …

Clostridioides difficile is a prominent cause of health care-related gastrointestinal illness in adults. C. difficile infection (CDI) has been researched for over 40 years; however, research on pediatric CDI specifically has lagged behind for various reasons. Over the past decade, C. difficile has b …

Phosphorylation is a post-translational modification that can affect both house-keeping functions and virulence characteristics in bacterial pathogens. In the Gram-positive enteropathogen Clostridioides difficile the extent and nature of phosphorylation events is poorly characterized, though a protein-kinase mutant strain demonstrates pleiotropic phenotypes. Here, we used an immobilized metal affinity chromatography strategy to characterize serine, threonine and tyrosine phosphorylation in C. difficile . We find limited protein phosphorylation in the exponential growth phase but a sharp increase in the number of phosphopeptides after the onset of stationary growth phase. Among the overall more than 1500 phosphosites, our approach identifies expected targets and phosphorylation sites, including the protein kinase PrkC, the anti-sigma-F factor antagonist (SpoIIAA), the anti-sigma-B factor antagonist (RsbV) and HPr kinase/phosphorylase (HprK). Analysis of high-confidence phosphosites shows that phosphorylation on serine residues is most common, followed by threonine and tyrosine phosphorylation. This work forms the basis for a further investigation into the contributions of individual kinases to the overall phosphoproteome of C. difficile and the role of phosphorylation in C. difficile physiology and pathogenesis.

Plasmids are ubiquitous in the bacterial world. In many microorganisms, plasmids have been implicated in important aspects of bacterial physiology and…

In this video, Paul Feuerstadt, MD, FACG, AGAF, discussed the annual incidence rate of Clostridioides difficile infection during and in the years preceding the COVID-19 pandemic.In 2011, health care-associated infections, as compared with community-associated infections, accounted for two-thirds of C. difficile infections, Feuerstadt, assistant clinical professor of medicine at Yale University,