C Diff Molecular

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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 …

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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.

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CDC/Jennifer Oosthuizen Medical illustration of Clostridioides difficile bacteria. FINDINGS Research led by scientists from UCLA and Harvard...

Research led by scientists from UCLA and Harvard University has uncovered details about how the bacterium Clostridioides difficile causes excessive

Inflammatory Bowel Disease (IBD) is not a true diagnosis. Rather, it encompasses a conglomeration of inflammatory digestive issues associated with a variety of causes. Patients often present with

What health care providers need to know about the 2 strains of C. difficile, including types of patients impacted and typical outcomes.

These reports include research on the impact of the microbiome on obesity, asthma and COVID-19.

Inflammation benefits C. diff in two ways: by suppressing competition and creating more resources for the bacterium.

A new peer-reviewed study reveals that the vast majority of U.S. infants may be suffering from a substantial deficiency in an important bacterium key to breast milk digestion and immune system development, ...

A discussion regarding the increasing frequency of C. difficile recurrence and its effects on patients and the health care system.

The inflammation caused by Clostridioides difficile (C. diff) infection gives the pathogen a two-fold advantage that helps it thrive, a new study shows.

Abdominal CT findings also predicted colitis during ICI cancer treatment

Colitis refers to the inflammation of the colon lining. There are different types of colitis that cause a range of symptoms. Learn more here.

A new study shows that the inflammation caused by Clostridioides difficile (C. diff) infection gives the pathogen a two-fold advantage: by both creating an inho

The microbiome-produced enzyme bile salt hydrolase (BSH) plays a central role in human health, but its function remains unclear due to the lack of suitable methods for measuring its activity. Here, we have developed a novel optical tool based on ultrasensitive bioluminescent imaging and demonstrated that this assay can be used for quick and cost-effective quantification of BSH activity across a broad range of biological settings including pure enzymes and bacteria, intact fecal slurries, and noninvasive imaging in live animals, as well as for the assessment of BSH activity in the entire gas...

The microbiome-produced enzyme bile salt hydrolase (BSH) plays a central role in human health, but its function remains unclear due to the lack of suitable methods for measuring its activity. Here, we have developed a novel optical tool based on ultrasensitive bioluminescent imaging and demonstrated that this assay can be used for quick and cost-effective quantification of BSH activity across a broad range of biological settings including pure enzymes and bacteria, intact fecal slurries, and noninvasive imaging in live animals, as well as for the assessment of BSH activity in the entire gas...

Patients with 3 or more C diff recurrences also had the highest health care resources utilization and total, all-cause, direct medical costs.

Clostridioides difficile thrives in an environment of inflammation which found that inflammation provides nutrients for C. diff and creates an inhospitable environment for competing bacteria.

Coronavirus disease 2019 is associated with a postinfectious multisystem inflammatory syndrome in children (MIS-C). This syndrome is marked by cytokine storm and multiorgan dysfunction, often affecting the gastrointestinal tract, the heart, and the hematopoietic system. We describe the case of a 16-year-old boy with an initial presentation of severe inflammatory bowel disease and concurrent MIS-C. He presented with abdominal pain, diarrhea, and hematochezia and met criteria for the systemic inflammatory response syndrome. Laboratory inflammatory profiling revealed markedly elevated ferritin...

Rates of serious clinical complications of Clostridioides difficile infection rose as the number of recurrent infections increased, underscoring the importance of advancing new treatments to prevent recurrence of the disease, a recent study in SAGE Open Medicine found.