262 results match your criteria activity tcda

Cwl0971, a novel peptidoglycan hydrolase, plays pleiotropic roles in Clostridioides difficile R20291.

Environ Microbiol 2021 Apr 24. Epub 2021 Apr 24.

Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.

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. Read More

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Proinflammatory Cytokines: Possible Accomplices for the Systemic Effects of Toxin B.

J Inflamm Res 2021 11;14:57-62. Epub 2021 Jan 11.

Gastroenterology, Hepatology & Digestive Endoscopy Section, Department of Medicine, University of Perugia Medical School, Perugia, Italy.

infection (CDI) has a serious impact on the healthcare system, and most of its pathogenic effects are mainly due to the activity of toxins A and B (TcdA and TcdB, respectively). The molecular mechanisms of their cytotoxic activity are well known, especially in the colon, where the infection occurs and normally remains localized. However, the mechanisms causing toxic effects on various systemic organs (extraintestinal manifestations) with frequent lethal outcomes in some patients affected by CDI are still poorly understood. Read More

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January 2021

Murine Intrarectal Instillation of Purified Recombinant Toxins Enables Mechanistic Studies of Pathogenesis.

Infect Immun 2021 Mar 17;89(4). Epub 2021 Mar 17.

Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

is linked to nearly 225,000 antibiotic-associated diarrheal infections and almost 13,000 deaths per year in the United States. Pathogenic strains of produce toxin A (TcdA) and toxin B (TcdB), which can directly kill cells and induce an inflammatory response in the colonic mucosa. Hirota et al. Read More

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Clostridium difficile toxin A and toxin B inhibit YAP in the colonic epithelial cells.

J Biochem Mol Toxicol 2021 Feb 30;35(2):e22652. Epub 2020 Nov 30.

Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Toxin A (TcdA) and toxin B (TcdB), the two exotoxins of Clostridium difficile, are main causal agents for the colonic epithelium damage in Clostridium difficile infection (CDI). The Hippo pathway is crucial for the control of tissue homeostasis and regeneration of intestines. However, the dysregulation of Hippo pathway in CDI is unclear. Read More

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February 2021

The glucosyltransferase activity of C. difficile Toxin B is required for disease pathogenesis.

PLoS Pathog 2020 09 22;16(9):e1008852. Epub 2020 Sep 22.

Department of Biochemistry, University of Toronto, and Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON, Canada.

Enzymatic inactivation of Rho-family GTPases by the glucosyltransferase domain of Clostridioides difficile Toxin B (TcdB) gives rise to various pathogenic effects in cells that are classically thought to be responsible for the disease symptoms associated with C. difficile infection (CDI). Recent in vitro studies have shown that TcdB can, under certain circumstances, induce cellular toxicities that are independent of glucosyltransferase (GT) activity, calling into question the precise role of GT activity. Read More

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September 2020

Novel Dietary Proteins Selectively Affect Intestinal Health In Vitro after -Secreted Toxin A Exposure.

Nutrients 2020 Sep 11;12(9). Epub 2020 Sep 11.

Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.

Bacterial gastroenteritis forms a burden on a global scale, both socially and economically. The Gram-positive bacterium is an inducer of gastrointestinal bacterial infections, often triggered following disruption of the microbiota by broad-spectrum antibiotics to treat other conditions. The clinical manifestatiaons, e. Read More

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September 2020

Human α-Defensin-5 Efficiently Neutralizes Toxins TcdA, TcdB, and CDT.

Front Pharmacol 2020 12;11:1204. Epub 2020 Aug 12.

Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany.

Infections with the pathogenic bacterium are coming more into focus, in particular in hospitalized patients after antibiotic treatment. produces the exotoxins TcdA and TcdB. Since some years, hypervirulent strains are described, which produce in addition the binary actin ADP-ribosylating toxin CDT. Read More

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The C-Terminal Domain of Clostridioides difficile TcdC Is Exposed on the Bacterial Cell Surface.

J Bacteriol 2020 10 22;202(22). Epub 2020 Oct 22.

Department of Medical Microbiology, Section Experimental Bacteriology, Leiden University Medical Center, Leiden, The Netherlands

is an anaerobic Gram-positive bacterium that can produce the large clostridial toxins toxin A and toxin B, encoded within the pathogenicity locus (PaLoc). The PaLoc also encodes the sigma factor TcdR, which positively regulates toxin gene expression, and TcdC, which is a putative negative regulator of toxin expression. TcdC is proposed to be an anti-sigma factor; however, several studies failed to show an association between the genotype and toxin production. Read More

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October 2020

Clostridioides difficile Toxin A Remodels Membranes and Mediates DNA Entry Into Cells to Activate Toll-Like Receptor 9 Signaling.

Gastroenterology 2020 12 22;159(6):2181-2192.e1. Epub 2020 Aug 22.

Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Background & Aims: Clostridioides difficile toxin A (TcdA) activates the innate immune response. TcdA co-purifies with DNA. Toll-like receptor 9 (TLR9) recognizes bacterial DNA to initiate inflammation. Read More

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December 2020

Microbiota in vitro modulated with polyphenols shows decreased colonization resistance against Clostridioides difficile but can neutralize cytotoxicity.

Sci Rep 2020 05 20;10(1):8358. Epub 2020 May 20.

National Laboratory for Health, Environment and Food, Prvomajska 1, 2000, Maribor, Slovenia.

While the knowledge on gut microbiota - C. difficile interactions has improved over the years, the understanding of the underlying mechanisms providing colonization resistance as well as preventative measures against the infection remain incomplete. In this study the antibiotic clindamycin and polyphenol extracts from pomegranate and blueberries were used individually and in combination to modulate fecal microbial communities in minibioreactor arrays (MBRA). Read More

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Human intestinal enteroids as a model of -induced enteritis.

Am J Physiol Gastrointest Liver Physiol 2020 05 30;318(5):G870-G888. Epub 2020 Mar 30.

Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas.

is an important nosocomial pathogen that produces toxins to cause life-threatening diarrhea and colitis. Toxins bind to epithelial receptors and promote the collapse of the actin cytoskeleton. toxin activity is commonly studied in cancer-derived and immortalized cell lines. Read More

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Structural elucidation of the transferase toxin reveals a single-site binding mode for the enzyme.

Proc Natl Acad Sci U S A 2020 03 2;117(11):6139-6144. Epub 2020 Mar 2.

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232;

is a Gram-positive, pathogenic bacterium and a prominent cause of hospital-acquired diarrhea in the United States. The symptoms of infection are caused by the activity of three large toxins known as toxin A (TcdA), toxin B (TcdB), and the transferase toxin (CDT). Reported here is a 3. Read More

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The Inflammasome and Type-2 Immunity in Infection.

Clin Colon Rectal Surg 2020 Mar 25;33(2):67-72. Epub 2020 Feb 25.

Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia.

(reclassified as " ") is the leading cause of hospital-acquired infections in the United States, and is associated with high-patient mortality and high rates of recurrence. Inflammasome priming and activation by the bacterial toxins, , , and transferase (CDT), initiates a potent immune response that is characterized by interleukin- (IL) 8, IL-1β, and neutrophil recruitment, and is required for pathogen killing. However, it is becoming clearer that a strong inflammatory response during infection can result in host tissue damage, and is associated with worse patient outcome. Read More

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Proteogenomic analysis of the Clostridium difficile exoproteome reveals a correlation between phylogenetic distribution and virulence potential.

Anaerobe 2020 Apr 13;62:102151. Epub 2020 Jan 13.

Centro de Investigación en Enfermedades Tropicales and Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica. Electronic address:

C. difficile induces antibiotic-associated diarrhea due to the action of two secreted toxins, TcdA and TcdB. A considerable range of virulence among C. Read More

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Small Molecule Inhibitor Screen Reveals Calcium Channel Signaling as a Mechanistic Mediator of TcdB-Induced Necrosis.

ACS Chem Biol 2020 05 14;15(5):1212-1221. Epub 2020 Jan 14.

Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, A4116A Medical Center North, 1161 21st Avenue South, Nashville, Tennessee 37232-2363, United States.

is the leading cause of nosocomial diarrhea in the United States. The primary virulence factors are two homologous glucosyltransferase toxins, TcdA and TcdB, that inactivate host Rho-family GTPases. The glucosyltransferase activity has been linked to a "cytopathic" disruption of the actin cytoskeleton and contributes to the disruption of tight junctions and the production of pro-inflammatory cytokines. Read More

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The xenobiotic sensing pregnane X receptor regulates tissue damage and inflammation triggered by C difficile toxins.

FASEB J 2020 02 17;34(2):2198-2212. Epub 2019 Dec 17.

Department of Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada.

Clostridioides difficile (formerly Clostridium difficile; C difficile), the leading cause of nosocomial antibiotic-associated colitis and diarrhea in the industrialized world, triggers colonic disease through the release two toxins, toxin A (TcdA) and toxin B (TcdB), glucosyltransferases that modulate monomeric G-protein function and alter cytoskeletal function. The initial degree of the host immune response to C difficile and its pathogenic toxins is a common indicator of disease severity and infection recurrence. Thus, targeting the intestinal inflammatory response during infection could significantly decrease disease morbidity and mortality. Read More

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February 2020

Designed Ankyrin Repeat Protein (DARPin) Neutralizers of TcdB from Clostridium difficile Ribotype 027.

mSphere 2019 10 2;4(5). Epub 2019 Oct 2.

Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, College Station, Texas, USA

infection (CDI) is a leading cause of hospital-acquired diarrhea. In recent decades, the emergence of the "hypervirulent" BI/NAP1/027 strains of significantly increased the morbidity and mortality of CDI. The pathogenesis of CDI is primarily mediated by the action of two toxins, TcdA and TcdB, with TcdB being the major virulent factor in humans. Read More

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October 2019

Antibacterial Activity of Against .

Front Cell Infect Microbiol 2019 7;9:288. Epub 2019 Aug 7.

State Key Laboratory of Microbial Metabolism, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

(YH68) is widely used in the fields of food fermentation and biomedicine. In this study, we explored the antibacterial activity of the cell free culture supernatant (CFCS) of YH68 against ATCC 9689 (CD) by measuring multiple indexes, including the growth, spores production, toxin A/B production, and the expression levels of the and genes of CD. In addition, we examined the changes in major cellular functional groups, structures, permeability, integrity, and the proton motive force (PMF) of the cytoplasmic membrane. Read More

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Phosphorylation and functionality of CdtR in Clostridium difficile.

Anaerobe 2019 Aug 16;58:103-109. Epub 2019 Jul 16.

Oral Microbiology Group, School of Dentistry and Institute of Microbiology and Infection, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, B5 7EG, UK.

The production of TcdA, TcdB and CDT in Clostridium difficile PCR ribotype 027, is regulated by the two-component system response regulator CdtR. Despite this, little is known about the signal transduction pathway leading to the activation of CdtR. In this study, we generated R20291ΔPalocΔcdtR model strains expressing CdtR phospho-variants in which our predicted phospho-accepting Asp, Asp61 was mutated for Ala or Glu. Read More

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Structure of the full-length Clostridium difficile toxin B.

Nat Struct Mol Biol 2019 08 15;26(8):712-719. Epub 2019 Jul 15.

Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.

Clostridium difficile is an opportunistic pathogen that establishes in the colon when the gut microbiota are disrupted by antibiotics or disease. C. difficile infection (CDI) is largely caused by two virulence factors, TcdA and TcdB. Read More

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Toxin B Variants from Strains VPI 10463 and NAP1/027 Share Similar Substrate Profile and Cellular Intoxication Kinetics but Use Different Host Cell Entry Factors.

Toxins (Basel) 2019 06 17;11(6). Epub 2019 Jun 17.

Facultad de Microbiología and Centro de Investigación en Enfermedades Tropicales, Universidad de Costa Rica, 10101 San José, Costa Rica.

induces antibiotic-associated diarrhea due to the release of toxin A (TcdA) and toxin B (TcdB), the latter being its main virulence factor. The epidemic strain NAP1/027 has an increased virulence attributed to different factors. We compared cellular intoxication by TcdB with that by the reference strain VPI 10463 (TcdB). Read More

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Enterotoxic Clostridia: Infections.

Microbiol Spectr 2019 05;7(3)

Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia, 3800.

is a Gram-positive, anaerobic, spore forming pathogen of both humans and animals and is the most common identifiable infectious agent of nosocomial antibiotic-associated diarrhea. Infection can occur following the ingestion and germination of spores, often concurrently with a disruption to the gastrointestinal microbiota, with the resulting disease presenting as a spectrum, ranging from mild and self-limiting diarrhea to severe diarrhea that may progress to life-threating syndromes that include toxic megacolon and pseudomembranous colitis. Disease is induced through the activity of the toxins TcdA and TcdB, both of which disrupt the Rho family of GTPases in host cells, causing cell rounding and death and leading to fluid loss and diarrhea. Read More

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Deciphering the domain specificity of C. difficile toxin neutralizing antibodies.

Vaccine 2019 06 20;37(29):3892-3901. Epub 2019 May 20.

Sanofi Pasteur, Research North America, 38 Sidney Street, Cambridge, MA 02139, USA. Electronic address:

Clostridium difficile infection (CDI) is the principal cause of nosocomial diarrhea and pseudomembranous colitis associated with antibiotic therapy. The pathological effects of CDI are primarily attributed to toxins A (TcdA) and B (TcdB). Adequate toxin-specific antibody responses are associated with asymptomatic carriage, whereas insufficient humoral responses are associated with recurrent CDI. Read More

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Shifts of Spatial Attention in Visual and Tactile Working Memory are Controlled by Independent Modality-Specific Mechanisms.

Cereb Cortex 2020 01;30(1):296-310

Department of Psychological Sciences, Birkbeck, University of London, London, UK.

The question whether the attentional control of working memory (WM) is shared across sensory modalities remains controversial. Here, we investigated whether attention shifts in visual and tactile WM are regulated independently. Participants memorized visual and tactile targets in a first memory sample set (S1) before encoding targets in a second sample set (S2). Read More

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January 2020

RstA Is a Major Regulator of Clostridioides difficile Toxin Production and Motility.

mBio 2019 03 12;10(2). Epub 2019 Mar 12.

Department of Microbiology and Immunology, Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia, USA

infection (CDI) is a toxin-mediated diarrheal disease. Several factors have been identified that influence the production of the two major toxins, TcdA and TcdB, but prior published evidence suggested that additional unknown factors were involved in toxin regulation. Previously, we identified a regulator, RstA, that promotes sporulation and represses motility and toxin production. Read More

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Differential effects of Clostridium difficile toxins on ion secretion and cell integrity in human intestinal cells.

Pediatr Res 2019 06 9;85(7):1048-1054. Epub 2019 Mar 9.

Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Naples, Italy.

Background: Toxin A (TcdA), toxin B (TcdB), and binary toxin (CDT) produced by Clostridium difficile (CD) are thought to play a key role in inducing diarrhea. The aim of this study was to investigate the individual and combined roles of CD toxins in inducing enterotoxic and cytotoxic effect.

Methods: Ion secretion and epithelial damage were evaluated in the Ussing chambers as measure of enterotoxic or cytotoxic effect, respectively, in human-derived intestinal cells. Read More

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Suppressive effect of Lactobacillus fermentum Lim2 on Clostridioides difficile 027 toxin production.

Lett Appl Microbiol 2019 May 24;68(5):386-393. Epub 2019 Mar 24.

Division of Animal Science, Chonnam National University, Gwangju, Korea.

Clostridioides difficile is a spore-forming, Gram-positive, anaerobic pathogen that caused gastrointestinal illness. During dysbiosis, overgrowth of C. difficile resulting in higher levels of toxin production. Read More

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Impact of CodY protein on metabolism, sporulation and virulence in Clostridioides difficile ribotype 027.

PLoS One 2019 30;14(1):e0206896. Epub 2019 Jan 30.

Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, United States of America.

Toxin synthesis and endospore formation are two of the most critical factors that determine the outcome of infection by Clostridioides difficile. The two major toxins, TcdA and TcdB, are the principal factors causing damage to the host. Spores are the infectious form of C. Read More

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September 2019

Cytotoxicity of Clostridium difficile toxins A and B requires an active and functional SREBP-2 pathway.

FASEB J 2019 04 28;33(4):4883-4892. Epub 2018 Dec 28.

Institut für Experimentelle and Klinische Pharmakologie und Toxikologie, Medizinische Fakultät, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany; and.

Clostridium difficile is associated with antibiotic-associated diarrhea and pseudomembranous colitis in humans. Its 2 major toxins, toxins A and B, enter host cells and inactivate GTPases of the Ras homologue/rat sarcoma family by glucosylation. Pore formation of the toxins in the endosomal membrane enables the translocation of their glucosyltransferase domain into the cytosol, and membrane cholesterol is crucial for this process. Read More

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PrsA2 (CD630_35000) of Is an Active Parvulin-Type PPIase and a Virulence Modulator.

Front Microbiol 2018 4;9:2913. Epub 2018 Dec 4.

Institut für Mikrobiologie, Technische Universität Braunschweig, Braunschweig, Germany.

is the main cause for nosocomial antibiotic associated diarrhea and has become a major burden for the health care systems of industrial countries. Its main virulence factors, the small GTPase glycosylating toxins TcdA and TcdB, are extensively studied. In contrast, the contribution of other factors to development and progression of infection (CDI) are only insufficiently understood. Read More

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December 2018