The anaerobic pathogen Clostridioides difficile is perfectly equipped to survive and persist inside the mammalian intestine. When facing unfavorable conditions C. difficile is able to form highly resistant endospores. Likewise, biofilms are currently discussed as form of persistence. H …

Cellobiose metabolism is linked to the virulence properties in numerous bacterial pathogens. Here, we characterized a putative cellobiose PTS operon of Clostridiodes difficile to investigate the role of cellobiose metabolism in C. difficile pathogenesis. Our gene knockout experiments demonstrated that the putative cellobiose operon enables uptake of cellobiose into C. difficile and allows growth when cellobiose is provided as the sole carbon source in minimal medium. Additionally, using reporter gene fusion assays and DNA pull-down experiments, we show that its transcription is regulated by CelR, a novel transcriptional repressor protein, which directly binds to the upstream region of the cellobiose operon to control its expression. We have also identified cellobiose metabolism to play a significant role in C. difficile physiology as observed by the reduction of sporulation efficiency when cellobiose uptake was compromised in the mutant strain. In corroboration to in vitro study findings, our in vivo hamster challenge experiment showed a significant reduction of pathogenicity by the cellobiose mutant strain in both the primary and the recurrent infection model- substantiating the role of cellobiose metabolism in C. difficile pathogenesis. ### Competing Interest Statement The authors have declared no competing interest.

Clostridioides difficile BI/NAP1/ribotype 027 is an epidemic hypervirulent strain found worldwide, including in Latin America. We examined the genomes and exoproteomes of two multilocus sequence type (MLST) clade 2 C. difficile strains considered hypervirulent: ICC-45 (ribotype SLO231/UK[CE]821), is …

This study found that ongoing exposure to PPIs was associated with a doubled risk of community-acquired Clostridium difficile infection. The risk was attenuated

C.difficile infection (CDI) is not a merely "gut-confined" disease as toxemia could drive the development of CDI-related extra-intestinal effects. These effects could explain the high CDI-associated mortality, not just justified by diarrhea and dehydration. Here, the extra-intestinal e …

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block immune inhibitory pathways. Administration of ICIs augments T cell-mediated immune responses against tumor, resulting in improved overall survival in cancer patients. It has emerged that the intestinal microbiome can modulate r …

Researchers at UCSF have found that extreme caloric restriction diets alter the microbiome in ways that could help with weight loss but might also result in an increased population of Clostridiodes difficile, a pathogenic bacterium that can lead to severe diarrhea and colitis.

The overall 90-day cumulative incidences of a first CDI episode was 1.9%.

On the HCPLive C. difficile condition center page, resources on the topics of medical news and expert insight into Clostridium difficile can be found. Content includes articles, interviews, videos, podcasts, and breaking news on C. diff research, treatment, and drug development.

Severe caloric restriction in humans leads to reversible changes in the gut microbiota that promote weight loss and the expansion of an enteric pathogen in mice.

The phosphorous balance is clinically important in increasing the long-term outcomes and preventing complications of end-stage renal disease. Sevelamer is a phosphate binder used widely to regulate hyperphosphatemia. On the other hand, gastrointestinal side effects increase with increasing sevelamer …

Researchers were able to show for the first time that a very low calorie diet significantly alters the composition of the microbiota present in the human gut. The researchers report that dieting results in an increase of specific bacteria - notably Clostridioides difficile, which is associated with antibiotic-induced diarrhea and colitis.

Antimicrobial resistance has become a worldwide problem due to its excessive increase in recent years. The aim of the present review was to bring together data from different articles describing the levels of antimicrobial resistance in the most common gastrointestinal infections reported across the …

Spore-forming pathogens like Clostridioides difficile depend on germination to initiate infection. Spore germination depends on the degradation of the protective spore peptidoglycan layer known as the spore cortex. Cortex degradation is mediated by enzymes that recognize the spore-specific peptidoglycan modification, muramic-∂-lactam (MAL). In C. difficile, MAL synthesis depends on the activity of the CwlD amidase and the GerS lipoprotein, which directly binds CwlD. To gain insight into how GerS regulates CwlD activity, we solved the crystal structure of the CwlD:GerS complex. In this structure, a GerS homodimer is bound to two CwlD monomers such that the CwlD active sites are exposed. Although CwlD structurally resembles amidase\_3 family members, we found that CwlD does not bind zinc stably on its own, unlike previously characterized amidase\_3 enzymes. Instead, GerS binding to CwlD promotes CwlD binding to zinc, which is required for its catalytic mechanism. Thus, in determining the first structure of an amidase bound to its regulator, we reveal stabilization of zinc co-factor binding as a novel mechanism for regulating bacterial amidase activity. Our results further suggest that allosteric regulation by binding partners may be a more widespread mode for regulating bacterial amidase activity than previously thought. ### Competing Interest Statement AS is a consultant and holds shares in a diagnostic start-up company, BioVector, Inc.

Clostridioides difficile infections are associated with gut microbiome dysbiosis and are the leading cause of hospital-acquired diarrhoea. The infectious process is strongly influenced by the microbiota and successful infection relies on the absence of specific microbiota-produced metabolites. Deoxy …

AbstractBackground. Clostridioides difficile was listed as an urgent antimicrobial resistance (AMR) threat in a report by the CDC in 2019. AMR drives the evolut

Clostridioides difficile (C. difficile) is classified as an urgent antibiotic resistance threat by the CDC. The 3-D structure shows how a key C. difficile toxin, TcdB (grey surface model), engages the human receptor CSPG4 (shown in green) for cell entry, and how an FDA-approved therapeutic antibody bezlotoxumab (shown in blue and purple) recognize two epitopes on TcdB. Some C. difficile hypervirulent strains evolve mutations in the bezlotoxumab-binding sites (blue and purple surface, while the mutated amino acids are colored red) that weaken the antibody potency. In contrast, the CSPG4-binding site on TcdB (gold surface) is highly conserved, suggesting a strategy to develop broad-spectrum therapeutics against TcdB.

Clostridioides difficile (C. difficile) infection is the most common cause of healthcare-associated infection and an important cause of morbidity and mortality among hospitalized patients. A comprehensive understanding of C. difficile infection (CDI) pathogenesis i …

Researchers observed the structure of a lethal toxin produced by certain strains of Clostridium difficile bacteria.

Clostridioides difficile is a noteworthy pathogen in patients with inflammatory bowel disease (IBD). Patients with IBD who develop concurrent C. difficile infection (CDI) experience increased morbidity and mortality. IBD is associated with intestinal inflammation and alterations of the gut microbiot …

There was no significant difference in performance between the model with only bile acids compared to models with bile acids and clinical variables.

Clostridioides difficile is the leading cause of healthcare-associated diarrhea worldwide following antibiotic treatment. Consequently, there is medical need for novel antibacterial agents acting against C. difficile that leave the resident microbiota unharmed. The development of such narrow-spectrum antibiotics requires precise knowledge of the mechanisms that fine-tune gene expression to orchestrate the genomic output at each locus in the genome. We address this issue by defining the global transcriptome architecture of C. difficile including noncoding regulatory elements, many of which are expressed during gut colonization. Our analysis of these regulators provides evidence for the global function of Hfq in sRNA binding and stabilization in a gram-positive bacterium. All RNA-sequencing data are available at the National Center for Biotechnology Information Gene Expression Omnibus database () under the accession number [GSE155167][1]. Plasmids pKJAK112, pJAK184, and pJAK080 have been deposited with Addgene ([167279][2]–[167281][3]). [1]: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE155167 [2]: https://www.addgene.org/167279/ [3]: https://www.addgene.org/167281/

Antimicrobial resistance (AMR) plays an important role in the pathogenesis and spread of Clostridioides difficile infection (CDI), the leading healthcare-related gastrointestinal infection in the world. An association between AMR and CDI outbreaks is well documented, however, data is limited to a few 'epidemic' strains in specific geographical regions. Here, through detailed analysis of 10,330 publicly-available C. difficile genomes from strains isolated worldwide (spanning 270 multilocus sequence types (STs) across all known evolutionary clades), this study provides the first species-wide snapshot of AMR genomic epidemiology in C. difficile . Of the 10,330 C. difficile genomes, 4,532 (43.9%) in 89 STs across clades 1 - 5 carried at least one genotypic AMR determinants, with 901 genomes (8.7%) carrying AMR determinants for three or more antimicrobial classes (multidrug-resistant, MDR). No AMR genotype was identified in any strains belonging to the cryptic clades. C. difficile from Australia/New Zealand had the lowest AMR prevalence compared to strains from Asia, Europe and North America (p

Clostridioides difficile is a noteworthy pathogen in patients with inflammatory bowel disease (IBD). Patients with IBD who develop concurrent C. difficile infection (CDI) experience increased morbidity and mortality. IBD is associated with intestinal inflammation and alterations of the gut microbiota, both of which can diminish colonization resistance to C. difficile. Here, we describe the development of a mouse model to explore the role that IBD-induced changes of the gut microbiome play in susceptibility to C. difficile. Helicobacter hepaticus, a normal member of the mouse gut microbiota, triggers pathological inflammation in the distal intestine akin to human IBD in mice that lack intact interleukin 10 (IL-10) signaling. We demonstrate that mice with H. hepaticus-induced IBD were susceptible to C. difficile colonization in the absence of other perturbations, such as antibiotic treatment. Concomitant IBD and CDI were associated with significantly worse disease than observed in animals with colitis alone. Development of IBD resulted in a distinct intestinal microbiota community compared to that of non-IBD controls. Inflammation played a critical role in the susceptibility of animals with IBD to C. difficile colonization, as mice colonized with an isogenic mutant of H. hepaticus that triggers an attenuated intestinal inflammation maintained full colonization resistance. These studies with a novel mouse model of IBD and CDI emphasize the importance of host responses and alterations of the gut microbiota in susceptibility to C. difficile colonization and infection in the setting of IBD. IMPORTANCE The incidence of C. difficile infection (CDI) has increased significantly among patients with IBD, independently of antibiotic use, yet the relationship between IBD and increased risk for CDI remains to be understood. Our study sought to describe and utilize an antibiotic-independent mouse model to specifically explore the relationship between the IBD-associated gut and susceptibility to C. difficile colonization and CDI development. We demonstrate that the development of IBD is sufficient to render mice susceptible to C. difficile colonization and results in significantly worse disease than IBD alone. Furthermore, this model requires IBD-induced inflammation to overcome colonization resistance to C. difficile. This model recapitulates human IBD and CDI comorbidity and will aid in developing new clinical approaches to predict, diagnose, and treat C. difficile infection in the IBD population.

Clostridioides difficile sequence type (ST) 37 (ribotype 017) is one of the most prevalent genotypes circulating in China. However, its genomic evolution and virulence determinants were rarely explored. Whole-genome sequencing, phylogeographic and phylogenetic analyses were conducted for C …

“C. diff. Spores and More” is an educational program providing you with up-to-date information pertaining to C. diff. and Healthcare-Associated infections.

In a recent study, researchers have found a significant positive association between vonoprazan use and Clostridioides difficile infection (CDI) ; however, they concluded that the magnitude of the...

Welcome to the European Society of Clinical Microbiology and Infectious Diseases - Study Group for Clostridioides difficile