C Diff Molecular

C Diff Molecular

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Allosteric activation of CwlD amidase activity by the GerS lipoprotein during Clostridioides difficile spore formation | bioRxiv
Allosteric activation of CwlD amidase activity by the GerS lipoprotein during Clostridioides difficile spore formation | bioRxiv
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.
·biorxiv.org·
Allosteric activation of CwlD amidase activity by the GerS lipoprotein during Clostridioides difficile spore formation | bioRxiv
Metabolic adaption to extracellular pyruvate triggers biofilm formation in Clostridioides difficile
Metabolic adaption to extracellular pyruvate triggers biofilm formation in Clostridioides difficile
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 …
·pubmed.ncbi.nlm.nih.gov·
Metabolic adaption to extracellular pyruvate triggers biofilm formation in Clostridioides difficile
3-D structure of C. difficile toxin engaged with CSPG4 receptor. - EurekAlert
3-D structure of C. difficile toxin engaged with CSPG4 receptor. - EurekAlert
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.
·eurekalert.org·
3-D structure of C. difficile toxin engaged with CSPG4 receptor. - EurekAlert
Integrating gut microbiome and host immune markers to understand the pathogenesis of Clostridioides difficile infection
Integrating gut microbiome and host immune markers to understand the pathogenesis of Clostridioides difficile infection
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 …
·pubmed.ncbi.nlm.nih.gov·
Integrating gut microbiome and host immune markers to understand the pathogenesis of Clostridioides difficile infection
Intestinal Inflammation and Altered Gut Microbiota Associated with Inflammatory Bowel Disease Render Mice Susceptible to Clostridioides difficile Colonization and Infection
Intestinal Inflammation and Altered Gut Microbiota Associated with Inflammatory Bowel Disease Render Mice Susceptible to Clostridioides difficile Colonization and Infection
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 …
·pubmed.ncbi.nlm.nih.gov·
Intestinal Inflammation and Altered Gut Microbiota Associated with Inflammatory Bowel Disease Render Mice Susceptible to Clostridioides difficile Colonization and Infection
An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important gram-positive bacterium | PNAS
An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important gram-positive bacterium | PNAS
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/
·pnas.org·
An RNA-centric global view of Clostridioides difficile reveals broad activity of Hfq in a clinically important gram-positive bacterium | PNAS
A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile | bioRxiv
A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile | bioRxiv
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
·biorxiv.org·
A species-wide genetic atlas of antimicrobial resistance in Clostridioides difficile | bioRxiv
Intestinal Inflammation and Altered Gut Microbiota Associated with Inflammatory Bowel Disease Render Mice Susceptible to Clostridioides difficile Colonization and Infection | mBio
Intestinal Inflammation and Altered Gut Microbiota Associated with Inflammatory Bowel Disease Render Mice Susceptible to Clostridioides difficile Colonization and Infection | mBio
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.
·journals.asm.org·
Intestinal Inflammation and Altered Gut Microbiota Associated with Inflammatory Bowel Disease Render Mice Susceptible to Clostridioides difficile Colonization and Infection | mBio
Genomic evolution and virulence association of Clostridioides difficile sequence type 37 (ribotype 017) in China()
Genomic evolution and virulence association of Clostridioides difficile sequence type 37 (ribotype 017) in China()
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 …
·pubmed.ncbi.nlm.nih.gov·
Genomic evolution and virulence association of Clostridioides difficile sequence type 37 (ribotype 017) in China()
C. diff. Spores and More C. diff. Spores and More
C. diff. Spores and More C. diff. Spores and More
“C. diff. Spores and More” is an educational program providing you with up-to-date information pertaining to C. diff. and Healthcare-Associated infections.
·voiceamerica.com·
C. diff. Spores and More C. diff. Spores and More
ESCMID: ESGCD
ESCMID: ESGCD
Welcome to the European Society of Clinical Microbiology and Infectious Diseases - Study Group for Clostridioides difficile
·escmid.org·
ESCMID: ESGCD
Major genetic discontinuity and novel toxigenic species in Clostridioides difficile taxonomy
Major genetic discontinuity and novel toxigenic species in Clostridioides difficile taxonomy
Clostridioides difficile infection (CDI) remains an urgent global One Health threat. The genetic heterogeneity seen across C. difficile underscores its wide ecological versatility and has driven the significant changes in CDI epidemiology seen in the last 20 years. We analysed an inter …
·pubmed.ncbi.nlm.nih.gov·
Major genetic discontinuity and novel toxigenic species in Clostridioides difficile taxonomy
Clostridioides difficile Infection and Liver Cirrhosis - A Retrospective, Cohort Study
Clostridioides difficile Infection and Liver Cirrhosis - A Retrospective, Cohort Study
Our study noted a more severe disease presentation and higher mortality in patients with cirrhosis admitted with CDI. Further studies are required for better understanding of the clinical course of CDI in cirrhosis and to evaluate the need for early intervention in this patient group.
·pubmed.ncbi.nlm.nih.gov·
Clostridioides difficile Infection and Liver Cirrhosis - A Retrospective, Cohort Study
Detection of Free Toxin B in the Stool of Asymptomatic Clostridioides difficile Carriers by the Cell Cytotoxicity Neutralization Assay
Detection of Free Toxin B in the Stool of Asymptomatic Clostridioides difficile Carriers by the Cell Cytotoxicity Neutralization Assay
Cell cytotoxicity neutralization assay (CCNA) is considered to be a gold standard to diagnose Clostridioides difficile infections. We performed CCNA on 77 consecutive admission screening rectal swabs from asymptomatic toxigenic C. difficile carriers. Thirty-nine percent of specimens fr …
·pubmed.ncbi.nlm.nih.gov·
Detection of Free Toxin B in the Stool of Asymptomatic Clostridioides difficile Carriers by the Cell Cytotoxicity Neutralization Assay
Outcomes of Immune Checkpoint Inhibitor-related Diarrhea or Colitis in Cancer Patients With Superimposed Gastrointestinal Infections - PubMed
Outcomes of Immune Checkpoint Inhibitor-related Diarrhea or Colitis in Cancer Patients With Superimposed Gastrointestinal Infections - PubMed
In our study, concomitant GI infections are associated with more severe symptoms in IMDC patients. Antimicrobial treatment did not circumvent the need for immunosuppressive therapy for IMDC or improve the clinical outcome. Concomitant GI infection was not associated with a higher risk of IMDC recurr …
·pubmed.ncbi.nlm.nih.gov·
Outcomes of Immune Checkpoint Inhibitor-related Diarrhea or Colitis in Cancer Patients With Superimposed Gastrointestinal Infections - PubMed
The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection
The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection
Clostridioides difficile infection (CDI) remains a major global cause of gastrointestinal infection, with significant associated morbidity, mortality and impact upon healthcare system resources. Recent antibiotic use is a key risk factor for the condition, with the marked antibiotic-mediated …
·pubmed.ncbi.nlm.nih.gov·
The contribution of bile acid metabolism to the pathogenesis of Clostridioides difficile infection
Clostridioides difficile specific DNA adenine methyltransferase CamA squeezes and flips adenine out of DNA helix
Clostridioides difficile specific DNA adenine methyltransferase CamA squeezes and flips adenine out of DNA helix
Clostridioides difficile infections are an urgent medical problem. The newly discovered C. difficile adenine methyltransferase A (CamA) is specified by all C. difficile genomes sequenced to date (>300), but is rare among other bacteria. CamA is an orphan methyltransferase, unassociated with a res …
·pubmed.ncbi.nlm.nih.gov·
Clostridioides difficile specific DNA adenine methyltransferase CamA squeezes and flips adenine out of DNA helix
Understanding the Microbiome | The Power of the Microbiome
Understanding the Microbiome | The Power of the Microbiome
The human microbiome has an important influence on metabolism and immunity. Learn more about how the power of the microbiome may be used to break the cycle of recurrent C diff, here.
·microbiome.ferring.com·
Understanding the Microbiome | The Power of the Microbiome