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Clostridium Difficile Toxin

Yaming Xi, Zhuanzhen Ma, Hao Zhang, Maowen Yuan, Lina Wang
The aim of the present study was to investigate the cytotoxic effect and multi-drug resistance (MDR) of Clostridium difficile toxin A (TcdA) on K562/A02 cells, and understand its underlying molecular pathways. K562/A02 cells were treated with TcdA at different concentrations for 24, 48 and 72 h, and the inhibition effect and drug resistance of TcdA on K562/A02 cell proliferation was assessed by methyl thiazolyl tetrazolium colorimetric assay. Furthermore, cell cycle-apoptosis was analyzed by flow cytometry, P-glycoprotein (P-gp) expression was determined by western blot analysis and caspase-3 activity was measured using a caspase-3 activity kit...
April 2018: Oncology Letters
Alan M McGovern, Grace O Androga, Peter Moono, Deirdre A Collins, Niki F Foster, Barbara J Chang, Thomas V Riley
Strains of Clostridium difficile producing only binary toxin (CDT) are found commonly in animals but not humans. However, human diagnostic tests rarely look for CDT. The Cepheid Xpert C. difficile BT assay detects CDT with equal sensitivity (≥92%) in human and animal faecal samples.
March 10, 2018: Anaerobe
Brunella Posteraro, Federico Pea, Luca Masucci, Patrizia Posteraro, Maurizio Sanguinetti
Clostridium difficile infection (CDI) is the most common healthcare-associated infection worldwide. As standard CDI antibiotic therapies can result in unacceptably high recurrence rates, novel therapeutic strategies for CDI are necessary. A recently emerged immunological therapy is a monoclonal antibody against C. difficile toxin B. Areas covered: In this review, the authors summarize the available pharmacological, preclinical, and clinical data for the CDI treatment based on anti-toxin A (actoxumab) and anti-toxin B (bezlotoxumab) human monoclonal antibodies (HuMabs), and discuss about the potentiality of a therapy that includes HuMab combined administration for CDI...
March 15, 2018: Expert Opinion on Biological Therapy
Natalia Blanco, Seth Walk, Anurag N Malani, Alexander Rickard, Michele Benn, Marisa Eisenberg, Min Zhang, Betsy Foxman
PURPOSE: This study aimed to describe the correlation between Clostridium difficile spore and toxin levels within the human host. In addition, we assessed whether overgrowth of Candida albicans modified this association. METHODOLOGY: We measured toxin, spore and Candida albicans levels among 200 successively collected stool samples that tested positive for C. difficile, and PCR ribotyped these C. difficile isolates. Analysis of variance and linear regression were used to test the association between spore and toxin levels...
March 13, 2018: Journal of Medical Microbiology
Anna Maikova, Johann Peltier, Pierre Boudry, Eliane Hajnsdorf, Nicolas Kint, Marc Monot, Isabelle Poquet, Isabelle Martin-Verstraete, Bruno Dupuy, Olga Soutourina
Clostridium difficile, a major human enteropathogen, must cope with foreign DNA invaders and multiple stress factors inside the host. We have recently provided an experimental evidence of defensive function of the C. difficile CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system important for its survival within phage-rich gut communities. Here, we describe the identification of type I toxin-antitoxin (TA) systems with the first functional antisense RNAs in this pathogen...
February 26, 2018: Nucleic Acids Research
Brintha Parasumanna Girinathan, Junjun Ou, Bruno Dupuy, Revathi Govind
Clostridium difficile is the primary cause of nosocomial diarrhea and pseudomembranous colitis. It produces dormant spores, which serve as an infectious vehicle responsible for transmission of the disease and persistence of the organism in the environment. In Bacillus subtilis, the sin locus coding SinR (113 aa) and SinI (57 aa) is responsible for sporulation inhibition. In B. subtilis, SinR mainly acts as a repressor of its target genes to control sporulation, biofilm formation, and autolysis. SinI is an inhibitor of SinR, so their interaction determines whether SinR can inhibit its target gene expression...
March 12, 2018: PLoS Pathogens
Klaus Aktories, Panagiotis Papatheodorou, Carsten Schwan
Clostridium difficile infection causes antibiotics-associated diarrhea and pseudomembranous colitis. Major virulence factors of C. difficile are the Rho-glucosylating toxins TcdA and TcdB. In addition, many, so-called hypervirulent C. difficile strains produce the binary actin-ADP-ribosylating toxin CDT. CDT causes depolymerization of F-actin and rearrangement of the actin cytoskeleton. Thereby, many cellular functions, which depend on actin, are altered. CDT disturbs the dynamic balance between actin and microtubules in target cells...
March 7, 2018: Anaerobe
Sara Andrés-Lasheras, Inma Martín-Burriel, Raúl Carlos Mainar-Jaime, Mariano Morales, Ed Kuijper, José L Blanco, Manuel Chirino-Trejo, Rosa Bolea
BACKGROUND: Clostridium difficile infection (CDI) is recognised as an emerging disease in both humans and some animal species. During the past few years, insights into human CDI epidemiology changed and C. difficile is also considered as an emerging community-acquired pathogen. Certain ribotypes (RT) are possibly associated with zoonotic transmission. The objective of this study was to assess the presence of C. difficile in a population of pets and to characterise the isolates. RESULTS: Faecal samples from a total of 90 diarrhoeic dogs and 24 from exotic animal species (both diarrhoeic and non-diarrhoeic) were analysed...
March 9, 2018: BMC Veterinary Research
Feng Liao, Wenge Li, Wenpeng Gu, Wenzhu Zhang, Xiaoshu Liu, Xiaoqing Fu, Wen Xu, Yuan Wu, Jinxing Lu
To identify the prevalence and characteristics of community-acquired Clostridium difficile infection (CA-CDI) in southwest China, we conducted a cross-sectional study. 978 diarrhea patients were enrolled and stool specimens' DNA was screened for virulence genes. Bacterial culture was performed and isolates were characterized by PCR ribotyping and multilocus sequence typing. Toxin genes tcdA and/or tcdB were found in 138/978 (14.11%) cases for fecal samples. A total of 55 C. difficile strains were isolated (5...
March 5, 2018: Scientific Reports
Yunli Zhang, Yanming Li, Hongling Li, Wei Chen, Wenen Liu
Clostridium difficile toxin B (cdtB) is a critical virulence factor characterized with potential cytotoxicity and pro-inflammatory activity. This study aims to investigate anti-tumor effects of cdtB on breast cancer development. Clostridium difficile strain was cultured and cdtB recombinant protein (rcdtB) was synthesized. Breast cancer cell line, MDA-MB-231, was divided into Normal control, rcdtB 50, 100, 200 and 400 ng/ml group in vitro. Mice were divided into Normal control and rcdtB treatment group (400 ng/ml) in vivo...
February 28, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Stojanović Predrag, Kocić Branislava, Stojanović Nikola, Radulovic Niko, Stojanović-Radić Zorica, Dobrila Stanković-Đorđević
Carriage of Clostridium (C.) difficile in the intestinum of children, as well as its role in the disease (diarrhea) onset, is still controversial. The aim of this study is to investigate the community-acquired Clostridium difficile infection (CA-CDI) in Serbian pediatric population and to describe the basic clinical characteristics and risk factors for CA-CDI occurrence in Serbian pediatric population. The data obtained from 63 Serbian pediatric patients with CA-CDI and from control group of 126 children with community-acquired diarrhea, whose stool specimens were negative for C...
March 1, 2018: European Journal of Clinical Microbiology & Infectious Diseases
S J Jin, K H Seo, Y M Wi
Management of Clostridium difficile infection (CDI) involves discontinuation of the offending antibiotic agent as soon as possible. However, the ongoing infection does not allow discontinuation of the offending antibiotic. We aimed to retrospectively investigate the predictors of treatment failure and impact of the concomitant use of systemic antibiotics in patients receiving metronidazole therapy. This study was conducted among patients hospitalised at a second care academic hospital from January 2013 to December 2014...
March 1, 2018: Epidemiology and Infection
F E Sachsenheimer, I Yang, O Zimmermann, C Wrede, L V Müller, K Gunka, U Groß, S Suerbaum
Infection with the emerging pathogen Clostridioides (Clostridium) difficile might lead to colonization of the gastrointestinal tract of humans and mammals eventually resulting in antibiotic-associated diarrhea, which can be mild to possibly life-threatening. Recurrences after antibiotic treatment have been described in 15-30% of the cases and are either caused by the original (relapse) or by new strains (reinfection). In this study, we describe a patient with ongoing recurrent C. difficile infections over 13 months...
February 21, 2018: International Journal of Medical Microbiology: IJMM
Ilana L Stroke, Jeffrey J Letourneau, Teresa E Miller, Yan Xu, Igor Pechik, Diana R Savoly, Linh Ma, Laurie J Sturzenbecker, Joan Sabalski, Philip D Stein, Maria L Webb, David W Hilbert
Clostridium difficile infection (CDI) is the leading cause of hospital-acquired infectious diarrhea, with significant morbidity, mortality and associated healthcare costs. The major risk factor for CDI is antimicrobial therapy, which disrupts the normal gut microbiota and allows C. difficile to flourish. Treatment of CDI with antimicrobials is generally effective in the short-term, but recurrent infections are frequent and problematic, indicating that improved treatment options are necessary. Symptoms of disease are largely due to two homologous toxins, TcdA and TcdB, which are glucosyltransferases that inhibit host Rho GTPases...
February 26, 2018: Antimicrobial Agents and Chemotherapy
Roy J Hopkins, Robert B Wilson
Clostridium difficile is a gram-positive, spore-forming, obligate anaerobic bacillus that was originally isolated from the stool of a healthy neonate in 1935. In high-income countries, C. difficile is the most common cause of infectious diarrhoea in hospitalized patients. The incidence of C. difficile infection in the USA has increased markedly since 2000, with hospitalizations for C. difficile infections in non-pregnant adults doubling between 2000 and 2010. Between 20% and 35% of patients with C. difficile infection will fail initial antibiotic treatment and, of these, 40-60% will have a second recurrence...
February 2018: Gastroenterology Report
Fabian K Berger, Sari S Rasheed, George F Araj, Rami Mahfouz, Hussein H Rimmani, Walid R Karaoui, Ala I Sharara, Ghassan Dbaibo, Sören L Becker, Lutz von Müller, Markus Bischoff, Ghassan M Matar, Barbara Gärtner
Clostridium (Clostridioides) difficile is the main cause for nosocomial diarrhoea in industrialised nations. Epidemiologic data on the pathogen's occurrence in other world regions are still scarce. In this context we characterized with phenotypic and molecular genetic methods C. difficile isolates stemming from hospitalised patients with diarrhoea in Lebanon. From 129 stool samples of symptomatic patients at a tertiary care University hospital in Lebanon, a total of 107 C. difficile strains were cultivated and underwent ribotyping, toxin gene detection and antibiotic resistance testing...
February 22, 2018: International Journal of Medical Microbiology: IJMM
Denise Rabold, Werner Espelage, Muna Abu Sin, Tim Eckmanns, Alexander Schneeberg, Heinrich Neubauer, Nadine Möbius, Katja Hille, Lothar H Wieler, Christian Seyboldt, Antina Lübke-Becker
BACKGROUND: Clostridium difficile infections (CDI) in humans range from asymptomatic carriage to life-threatening intestinal disease. Findings on C. difficile in various animal species and an overlap in ribotypes (RTs) suggest potential zoonotic transmission. However, the impact of animals for human CDI remains unclear. METHODS: In a large-scale survey we collected 1,447 fecal samples to determine the occurrence of C. difficile in small companion animals (dogs and cats) and their owners and to assess potential epidemiological links within the community...
2018: PloS One
Fenfen Zhou, Therwa Hamza, Ashley S Fleur, Yongrong Zhang, Hua Yu, Kevin Chen, Jonathon E Heath, Ye Chen, Haihui Huang, Hanping Feng
Background: Over the past several decades, there has been a significant increase in the incidence of Clostridium difficile infection (CDI) in patients suffering from inflammatory bowel disease (IBD). However, a wild-type animal model is not available to study these comorbid diseases. Methods: We evaluated the susceptibility to CDI of mice with dextran sulfate sodium salt (DSS)-induced colitis (IBD mice) with or without antibiotic exposure; we examined the histopathology and cytokine response in the concomitant diseases after the model was created...
February 15, 2018: Inflammatory Bowel Diseases
Donna M Schora, Lance R Peterson, Elena A Usacheva
OBJECTIVE The impact of storage on stability and detection of Clostridium difficile toxins in feces is poorly understood. The objective of this study was to investigate the immunological stability of C. difficile toxins in clinical stool specimens under different storage conditions by evaluating this stability using toxin detection by enzyme immunoassay (EIA). METHODS Stool specimens positive for C. difficile infection (CDI) by quantitative polymerase chain reaction (qPCR) were used for EIA testing with the C...
February 19, 2018: Infection Control and Hospital Epidemiology
James A Karlowsky, Heather J Adam, Tyler Kosowan, Melanie R Baxter, Kim A Nichol, Nancy M Laing, George Golding, George G Zhanel
Clostridium difficile toxin-positive diarrheal stool specimens submitted to eight Canadian hospital laboratories from 2013 to 2015 were cultured. Polymerase chain reaction ribotyping of isolates was performed using an internationally standardized, high-resolution capillary gel-based electrophoresis protocol and antimicrobial susceptibility testing conducted by CLSI-defined agar dilution (M11-A8, 2012). Among the 1310 isolates of C. difficile cultured, 141 different ribotypes were identified; the most common ribotypes were 027 (24...
January 31, 2018: Diagnostic Microbiology and Infectious Disease
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