SATB2 plays a vital role in maintaining intestinal homeostasis and its deficiency promotes the development of colitis and CAC by influencing the intestinal luminal environment and gut flora.

These data suggest that fecal microbiota from children with VA deficiency attenuates colonic barrier function in GF mice, which may be achieved by changing the bile acid metabolic pathways.

Clostridioides difficile is a Gram-positive, spore-forming, toxin-producing anaerobe that can cause nosocomial antibiotic-associated intestinal disease. Although the production of toxin A (TcdA) and toxin B (TcdB) contribute to the main pathogenesis of C. difficile , the mechanism of TcdA and TcdB release from cell remains unclear. In this study, we identified and characterized a new cell wall hydrolase Cwl0971 ( CDR20291_0971 ) from C. difficile R20291, which is involved in bacterial autolysis. The gene 0971 deletion mutant (R20291Δ0971) generated with CRISPR-AsCpfI exhibited significantly delayed cell autolysis and increased cell viability compared to R20291, and the purified Cwl0971 exhibited hydrolase activity for Bacillus subtilis cell wall. Meanwhile, 0971 gene deletion impaired TcdA and TcdB release due to the decreased cell autolysis in the stationary / late phase of cell growth. Moreover, sporulation of the mutant strain decreased significantly compared to the wild type strain. In vivo , the defect of Cwl0971 decreased fitness over the parent strain in a mouse infection model. Collectively, Cwl0971 is involved in cell wall lysis and cell viability, which affects toxin release, sporulation, germination, and pathogenicity of R20291, indicating that Cwl0971 could be an attractive target for C. difficile infection therapeutics and prophylactics. ### Competing Interest Statement The authors have declared no competing interest.

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A temperate siphovirus, phiCDKH01, was obtained from a clinical isolate of Clostridioides difficile. The phage genome is a 45,089-bp linear double-stranded DNA molecule with an average G+C content of 28.7%. It shows low similarity to known phage genomes, except for phiCD24-1. Genomic and phylogeneti …

Constipation affects approximately 60% of patients with diabetes and 16% of adults overall. This story breaks down treatments and related conditions.

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

Comparative analysis of Clostridioides difficile whole-genome sequencing (WGS) data enables fine scaled investigation of transmission and is increasingly becoming part of routine surveillance. However, these analyses are constrained by the computational requirements of the large volumes of data involved. By decomposing WGS reads or assemblies into k-mers and using the dimensionality reduction technique MinHash, it is possible to rapidly approximate genomic distances without alignment. Here we assessed the performance of MinHash, as implemented by sourmash, in predicting single nucleotide differences between genomes (SNPs) and C. difficile ribotypes (RTs). For a set of 1,905 diverse C. difficile genomes (differing by 0-168,519 SNPs), using sourmash to screen for closely related genomes, at a sensitivity of 100% for pairs ≤10 SNPs, sourmash reduced the number of pairs from 1,813,560 overall to 161,934, i.e., by 91%, with a positive predictive value of 32% to correctly identify pairs ≤10 SNPs (maximum SNP distance 4,144). At a sensitivity of 95%, pairs were reduced by 94% to 108,266 and PPV increased to 45% (maximum SNP distance 1,009). Increasing the MinHash sketch size above 2000 produced minimal performance improvement. We also explored a MinHash similarity-based ribotype prediction method. Genomes with known ribotypes (n=3,937) were split into a training set (2,937) and test set (1,000) randomly. The training set was used to construct a sourmash index against which genomes from the test set were compared. If the closest 5 genomes in the index had the same ribotype this was taken to predict the searched genome’s ribotype. Using our MinHash ribotype index, predicted ribotypes were correct in 780/1000 (78%) genomes, incorrect in 20 (2%), and indeterminant in 200 (20%). Relaxing the classifier to 4/5 closest matches with the same RT improved the correct predictions to 87%. Using MinHash it is possible to subsample C. difficile genome k-mer hashes and use them to approximate small genomic differences within minutes, significantly reducing the search space for further analysis. Impact statement The genetic code, or DNA, of bacteria is increasingly used to track how infection spreads and to guide infection control interventions, as similar or identical DNA sequences are expected in samples from pair of individuals related by transmission. While obtaining the DNA sequence for bacteria is increasingly straightforward, comparing thousands or even millions of sequences requires substantial computing power and time using current approaches. Here we describe how a method for summarising sequencing data, MinHash, can be used to rapidly reduce the number of possible close sequence matches in Clostridioides difficile , an important healthcare-associated pathogen. It can also be used to approximate traditional schemes used to classify C. difficile into smaller subgroups in transmission analyses, such as ribotyping. Data summary The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files. ### Competing Interest Statement MHW has received consulting fees from Actelion, Astellas, MedImmune, Merck, Pfizer, Sanofi-Pasteur, Seres, Summit, and Synthetic Biologics; lecture fees from Alere, Astellas, Merck & Pfizer; and grant support from Actelion, Astellas, bioMerieux, Da Volterra, Merck and Summit. SDG has received consulting fees from Abbott, Aquarius Population Health, Astellas and MSD; lecture fees from Astellas, MSD and Orion Diagnostics; and grant support from Astellas. DWE declares lecture fees from Gilead outside the submitted work. No other author has a conflict of interest to declare.

Cell growth and division require a balance between synthesis and hydrolysis of the peptidoglycan (PG). Inhibition of PG synthesis or uncontrolled PG hydrolysis can be lethal for the cells, making it imperative to control peptidoglycan hydrolase (PGH) activity. The synthesis or activity of several ke …

The pathogenesis of Clostridioides difficile infection (CDI) has largely been attributed to the action of two major toxins - A and B. An enhanced systemic humoral immune response against these toxins has been shown to be protective against recurrent CDI. Over the years, fully human monoclonal …

In this narrative review, we synthetize current knowledge on several infections including urinary tract infection, pneumonia, Helicobacter pylori, coronavirus disease 2019, and Clostridioides difficile as they relate to NAFLD

The results of this study showed toxigenic C. difficile with tcdA + /tcdB + profile is a major cause of nosocomial diarrhea in Hamadan, and clinical laboratories should routinely perform C. difficile diagnostic testing on diarrheal specimens of hospi …

Seres Therapeutics, Inc. (Nasdaq: MCRB), a leading microbiome therapeutics company, today announced that it will present recent research findings from its microbiome drug development portfolio at Digestive Disease Week® (DDW), which is taking place virtually from May 21-23, 2021. With two oral presentations and two posters of distinction, Seres will demonstrate the potential of microbiome-based therapies for patients with serious diseases like recurrent Clostridioides difficile infection (CDI) and ulcerative colitis (UC).

The gut bacterial community prevents many pathogens from colonizing the intestine. Previous studies have associated specific bacteria with clearing Clostridioides difficile colonization across different community perturbations. However, those bacteria alone have been unable to clear C. dif …

Females and older patients had higher rates of hospitalizations with CDI than males and younger patients.

Colonization by the microbiota provides one of our most effective barriers against infection by pathogenic microbes. The microbiota protects against infection by priming immune defenses, by metabolic exclusion of pathogens from their preferred niches, and through direct antimicrobial antagonism. Dis …

The introduction of stable isotopes in vivo via metabolic labeling approaches (SILAC or 15N-labeling) allows, after combination of differentially treated labeled and unlabeled cells or protein extracts, for correction of protein quantification errors implemented during elaborated sample p …

Clostridioides difficile is a Gram positive spore-forming rod and mainly responsible for nosocomial diarrhea in developed nations. Molecular and antimicrobial surveillance is important for monitoring the strain composition including genotypes of high epidemiological importance such as ribotype 027 ( …

Approximately 5000 of the 276,000 deaths that occur annually among hospitalized adults in England can be attributed to AGE not caused by CDI, which is higher than previously estimated.

We have identified and characterised a cortex specific PBP in C. difficile. This is the first characterisation of a cortex-specific PBP in C. difficile and begins the process of unravelling cortex biogenesis in this important pathogen.

Surveying new biomedical words listed in the Oxford English Dictionary (OED) since 1970, I have found fewer examples each year. For example, the 1970 list contained 61 words and the [...]More...