scholarly journals Difference in Mono-O-Glucosylation of Ras Subtype GTPases Between Toxin A and Toxin B From Clostridioides difficile Strain 10463 and Lethal Toxin From Clostridium sordellii Strain 6018

2018 ◽  
Vol 9 ◽  
Author(s):  
Harald Genth ◽  
Johannes Junemann ◽  
Chantal M. Lämmerhirt ◽  
Arlen-Celina Lücke ◽  
Ilona Schelle ◽  
...  
Keyword(s):  
Lethal Toxin ◽  
Toxin A ◽  
Toxin B ◽  
Clostridium Sordellii ◽  
Clostridioides Difficile

A novel fusion protein containing the receptor binding domains of C. difficile toxin A and toxin B elicits protective immunity against lethal toxin and spore challenge in preclinical efficacy models

Vaccine ◽  
2012 ◽  
Vol 30 (28) ◽  
pp. 4249-4258 ◽  
Author(s):  
Jing-Hui Tian ◽  
Steven R. Fuhrmann ◽  
Stefanie Kluepfel-Stahl ◽  
Robert J. Carman ◽  
Larry Ellingsworth ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Receptor Binding ◽  
Protective Immunity ◽  
Lethal Toxin ◽  
Toxin A ◽  
Toxin B ◽  
Binding Domains ◽  
Preclinical Efficacy

scholarly journals Host Immune Markers Distinguish Clostridioides difficile Infection From Asymptomatic Carriage and Non–C. difficile Diarrhea

2019 ◽  
Author(s):  
Ciaran P Kelly ◽  
Xinhua Chen ◽  
David Williams ◽  
Hua Xu ◽  
Christine A Cuddemi ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Symptomatic Patient ◽  
Nucleic Acid Amplification ◽  
Toxin A ◽  
Toxin B ◽  
Innate And Adaptive Immunity ◽  
Clostridioides Difficile ◽  
Asymptomatic Carriage ◽  
Positive Stool ◽  
Tnf Α

Abstract Background Recent data indicate that Clostridioides difficile toxin concentrations in stool do not differentiate between C. difficile infection (CDI) and asymptomatic carriage. Thus, we lack a method to distinguish a symptomatic patient with CDI from a colonized patient with diarrhea from another cause. To address this, we evaluated markers of innate and adaptive immunity in adult inpatients with CDI (diagnosed per US guidelines), asymptomatic carriage, or non-CDI diarrhea. Methods CDI-NAAT patients had clinically significant diarrhea and positive nucleic acid amplification testing (NAAT) and received CDI treatment. Carrier-NAAT patients had positive stool NAAT but no diarrhea. NAAT-negative patients (with and without diarrhea) were also enrolled. A panel of cytokines and anti–toxin A and B immunoglobulin (Ig) were measured in serum; calprotectin and anti–toxin B Ig A/G were measured in stool. NAAT-positive stool samples were tested by an ultrasensitive toxin assay (clinical cutoff, 20 pg/mL). Results Median values for interleukin (IL)-4, IL-6, IL-8, IL-10, IL-15, granulocyte colony-stimulating factor (GCSF), MCP-1, tumor necrosis factor α (TNF-α), and IgG anti–toxin A in blood and IgA/G anti–toxin B in stool were significantly higher in CDI patients compared with all other groups (P < .05). Concentration distributions for IL-6, GCSF, TNF-α, and IgG anti–toxin A in blood, as well as IgA and IgG anti–toxin B in stool, separated CDI patients from all other groups. Conclusions Specific markers of innate and adaptive immunity distinguish CDI from all other groups, suggesting potential clinical utility for identifying which NAAT- and toxin-positive patients with diarrhea truly have CDI.

scholarly journals Toxin A–Predominant Pathogenic Clostridioides difficile: A Novel Clinical Phenotype

2019 ◽  
Vol 70 (12) ◽  
pp. 2628-2633 ◽  
Author(s):  
Qianyun Lin ◽  
Nira R Pollock ◽  
Alice Banz ◽  
Aude Lantz ◽  
Hua Xu ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Toxin Production ◽  
Toxin A ◽  
Toxin B ◽  
Clostridioides Difficile ◽  
Quantitative Immunoassay ◽  
Clinical Detection ◽  
Stool Samples

Abstract Background Most Clostridioides difficile toxinogenic strains produce both toxins A and B (A+B+), but toxin A–negative, toxin B–positive (A−B+) variants also cause disease. We report the identification of a series of pathogenic clinical C. difficile isolates that produce high amounts of toxin A with low or nondetectable toxin B. Methods An ultrasensitive, quantitative immunoassay was used to measure toxins A and B in stool samples from 187 C. difficile infection (CDI) patients and 44 carriers. Isolates were cultured and assessed for in vitro toxin production and in vivo phenotypes (mouse CDI model). Results There were 7 CDI patients and 6 carriers who had stools with detectable toxin A (TcdA, range 23–17 422 pg/mL; 5.6% of samples overall) but toxin B (TcdB) below the clinical detection limit (&lt;20 pg/mL; median TcdA:B ratio 17.93). Concentrations of toxin A far exceeded B in in vitro cultures of all 12 recovered isolates (median TcdA:B ratio 26). Of 8 toxin A&gt;&gt;B isolates tested in mice, 4 caused diarrhea, and 3 of those 4 caused lethal disease. Ribotyping demonstrated strain diversity. TcdA-predominant samples were also identified at 2 other centers, with similar frequencies (7.5% and 6.8%). Conclusions We report the discovery of clinical pathogenic C. difficile strains that produce high levels of toxin A but minimal or no toxin B. This pattern of toxin production is not rare (&gt;5% of isolates) and is consistently observed in vitro and in vivo in humans and mice. Our study highlights the significance of toxin A in human CDI pathogenesis and has important implications for CDI diagnosis, treatment, and vaccine development.

scholarly journals Detoxification of toxin A and toxin B by copper ion-catalyzed oxidation in production of a toxoid-based vaccine against Clostridioides difficile

2020 ◽  
Vol 160 ◽  
pp. 433-446
Author(s):  
Aria Aminzadeh ◽  
Manish Kumar Tiwari ◽  
Srwa Satar Mamah Mustapha ◽  
Sandra Junquera Navarrete ◽  
Anna Bielecka Henriksen ◽  
...  
Keyword(s):  
Copper Ion ◽  
Toxin A ◽  
Toxin B ◽  
Clostridioides Difficile ◽  
Catalyzed Oxidation

scholarly journals Systematic Evaluation of Parameters Important for Production of Native Toxin A and Toxin B from Clostridioides difficile

Toxins ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 240
Author(s):  
Aria Aminzadeh ◽  
René Jørgensen
Keyword(s):  
Sandwich Elisa ◽  
Toxin Production ◽  
Culture Conditions ◽  
Systematic Evaluation ◽  
Toxin A ◽  
Toxin B ◽  
Melting Temperatures ◽  
Clostridioides Difficile ◽  
Differential Scanning Fluorimetry ◽  
Yeast Extract Medium

In the attempt to improve the purification yield of native toxin A (TcdA) and toxin B (TcdB) from Clostridioides difficile (C. difficile), we systematically evaluated culture parameters for their influence on toxin production. In this study, we showed that culturing C. difficile in a tryptone-yeast extract medium buffered in PBS (pH 7.5) that contained 5 mM ZnCl2 and 10 mM glucose supported the highest TcdB production, measured by the sandwich ELISA. These culture conditions were scalable into 5 L and 15 L dialysis tube cultures, and we were able to reach a TcdB concentration of 29.5 µg/mL of culture. Furthermore, we established a purification protocol for TcdA and TcdB using FPLC column chromatography, reaching purities of >99% for both toxins with a yield around 25% relative to the starting material. Finally, by screening the melting temperatures of TcdA and TcdB in various buffer conditions using differential scanning fluorimetry, we found optimal conditions for improving the protein stability during storage. The results of this study present a complete protocol for obtaining high amounts of highly purified native TcdA and TcdB from C. difficile.

scholarly journals Infection with Toxin A-Negative, Toxin B-Negative, Binary Toxin-Positive Clostridium difficile in a Young Patient with Ulcerative Colitis

2015 ◽  
Vol 53 (11) ◽  
pp. 3702-3704 ◽  
Author(s):  
Grace O. Androga ◽  
Julie Hart ◽  
Niki F. Foster ◽  
Adrian Charles ◽  
David Forbes ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clostridium Difficile ◽  
Young Patient ◽  
Diagnostic Methods ◽  
Binary Toxin ◽  
Toxin A ◽  
Toxin B ◽  
Content Type ◽  
Severe Diarrhea ◽  
Clinically Significant

Large clostridial toxin-negative, binary toxin-positive (A−B−CDT+) strains ofClostridium difficileare almost never associated with clinically significantC. difficileinfection (CDI), possibly because such strains are not detected by most diagnostic methods. We report the isolation of an A−B−CDT+ribotype 033 (RT033) strain ofC. difficilefrom a young patient with ulcerative colitis and severe diarrhea.

Sign in / Sign up

Export Citation Format

Share Document