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Clostridium Difficile Toxin

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https://www.readbyqxmd.com/read/28433497/clostridium-difficile-toxin-glucosyltransferase-domains-in-complex-with-a-non-hydrolyzable-udp-glucose-analogue
#1
Joseph W Alvin, D Borden Lacy
Clostridium difficile is the leading cause of hospital-acquired diarrhea and pseudomembranous colitis worldwide. The organism produces two homologous toxins, TcdA and TcdB, which enter and disrupt host cell function by glucosylating and thereby inactivating key signalling molecules within the host. As a toxin-mediated disease, there has been a significant interest in identifying small molecule inhibitors of the toxins' glucosyltransferase activities. This study was initiated as part of an effort to identify the mode of inhibition for a small molecule inhibitor of glucosyltransferase activity called apigenin...
April 19, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28431238/reducing-recurrence-of-c-difficile-infection
#2
Michael G Dieterle, Vincent B Young
Clostridium difficile infection (CDI) is facilitated by alteration of the microbiome following antibiotic administration. Antimicrobial therapy directed against the pathogen can treat CDI. Unfortunately, ∼20% of successfully treated patients will suffer recurrence. Bezlotoxumab, a human monoclonal antibody, binds to C. difficile toxin B (TcdB), reducing recurrence presumably by limiting epithelial damage and facilitating microbiome recovery.
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28401147/toxinotyping-and-sequencing-of-clostridium-difficile-isolates-from-patients-in-a-tertiary-care-hospital-of-northern-india
#3
Meenakshi Singh, Chetana Vaishnavi, Safrun Mahmood, Rakesh Kochhar
BACKGROUND: Clostridium difficile is an important cause of infectious colitis among hospitalized patients across the globe. The pathogenic potential of C. difficile in producing significant morbidity and mortality is mainly due to production of toxins A and B. The outbreaks of C. difficile infection (CDI) are due to changes in the genetic sequences of the organism. There is hardly any molecular study reported on the prevalent types of C. difficile strains in India. Toxinotyping and sequencing of locally circulating C...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28396132/clostridium-difficile-infection
#4
REVIEW
Luis Alcalá Hernández, Elena Reigadas Ramírez, Emilio Bouza Santiago
Clostridium difficile infection (CDI) is the main cause of nosocomial diarrhea in industrialized countries and the source of a growing number of cases of diarrhea in the community. The outbreak of the hypervirulent strain belonging to ribotype 027 has increased the incidence and severity of CDI in some countries. Although CDI usually courses as a mild diarrhea it can lead to severe forms such as toxic megacolon or septic shock. One of every 2 episodes of CDI is not diagnosed in Spanish hospitals due to a lack of clinical suspicion or the use of insensitive diagnostic methods...
April 8, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28389190/detection-of-vancomycin-resistant-enterococci-vre-in-stool-specimens-submitted-for-clostridium-difficile-toxin-testing
#5
Sevim Özsoy, Arzu İlki
The aim of this study was to determine the association between Clostridium difficile (C. difficile) and vancomycin-resistant Enterococcus (VRE) and efficacy of screening stools submitted for C. difficile toxin assay for prevalence of VRE. Between April 2012 and February 2014, 158 stool samples submitted for C. difficile toxin to the Marmara University Microbiology Laboratory, were included in the study. Stool samples were analyzed by enzyme immuno assay test; VIDAS (bioMerieux, France) for Toxin A&B. Samples were inoculated on chromID VRE (bioMerieux, France) and incubated 24h at 37°C...
March 17, 2017: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/28385835/genome-sequence-of-a-toxin-positive-clostridium-difficile-strain-isolated-from-murine-feces
#6
Lucie Etienne-Mesmin, Benoit Chassaing, Oluwaseyi Adekunle, Lisa M Mattei, Adrianne N Edwards, Shonna M McBride, Frederic D Bushman, Andrew T Gewirtz
Herein, we report the genome sequence of a Clostridium difficile strain isolated from the feces of antibiotic-treated C57BL/6 mice. We have named this strain, which differs considerably from those of the previously sequenced C. difficile strains, LEM1.
April 6, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28366569/development-of-a-dose-assay-for-a-clostridium-difficile-vaccine-using-a-tandem-ion-exchange-high-performance-liquid-chromatography-method
#7
Feng Wang, Sha Ha, Richard R Rustandi
Clostridium difficile is a gram-positive intestine bacterium that causes a severe diarrhea and could eventually be lethal. The main virulence factor is related to the release of two major exotoxins, toxin A (TcdA) and toxin B (TcdB). Recent C. difficile-associated disease (CDAD) outbreaks have been caused by hypervirulent strains which secrete an additional binary toxin (CDTa/CDTb). Vaccination against these toxins is considered the best way to combat the CDAD. Recently, a novel tetravalent C. difficile vaccine candidate containing all four toxins produced from a baculovirus expression system has been developed...
March 21, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28360030/old-and-new-models-for-studying-host-microbe-interactions-in-health-and-disease-c-difficile-as-an-example
#8
Vincent Bensan Young
There has been an explosion of interest in studying the indigenous microbiota, which plays an important role in human health and disease. Traditionally, the study of microbes in relationship to human health involved consideration of individual microbial species that caused classical infectious diseases. With the interest in the human microbiome, an appreciation of the influence that complex communities of microbes can have on their environment has developed. When considering either individual pathogenic microbes or a symbiotic microbial community, researchers have employed a variety of model systems with which they can study the host-microbe interaction...
March 30, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28355613/clostridium-difficile-infection-in-returning-travellers
#9
A Michal Stevens, Douglas H Esposito, Rhett J Stoney, Davidson H Hamer, Jose Flores-Figueroa, Emmanuel Bottieau, Bradley A Connor, Effrossyni Gkrania-Klotsas, Abraham Goorhuis, Noreen A Hynes, Michael Libman, Rogelio Lopez-Velez, Anne E McCarthy, Frank von Sonnenburg, Eli Schwartz, Perry J J van Genderen, L Scott Benson, Daniel T Leung
Background: There is increasing recognition of the contribution of community-acquired cases to the global burden of Clostridium difficile infection (CDI). The epidemiology of CDI among international travellers is poorly understood, and factors associated with international travel, such as antibiotic use and changes in gut microbiota, could potentially put travellers at higher risk. Methods: We summarized demographic, travel-associated and geographic characteristics of travellers with CDI in the GeoSentinel database from 1997 to 2015...
May 1, 2017: Journal of Travel Medicine
https://www.readbyqxmd.com/read/28355266/molecular-epidemiology-and-antimicrobial-susceptibility-of-clostridium-difficile-isolates-from-two-korean-hospitals
#10
Asiimwe Nicholas, Yu Kyung Kim, Won-Kil Lee, Gati Noble Selasi, Seok Hyeon Na, Hyo Il Kwon, Yoo Jeong Kim, Hae Sook Lee, Kyung Eun Song, Jeong Hwan Shin, Je Chul Lee
Clostridium difficile is one of the main etiological agents causing antibiotic-associated diarrhea. This study investigated the genetic diversity of 70 toxigenic C. difficile isolates from two Korean hospitals by employing toxinotyping, ribotyping, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Toxin gene amplification resulted in 68 A⁺B⁺ and two A-B+ isolates. Most isolates (95.7-100%) were susceptible to daptomycin, metronidazole, and vancomycin. Seventy C. difficile isolates were classified into five toxinotypes, 19 ribotypes, 16 sequence types (STs), and 33 arbitrary pulsotypes...
2017: PloS One
https://www.readbyqxmd.com/read/28353450/predominance-of-clostridium-difficile-027-during-a-five-year-period-in-bolzano-northern-italy
#11
Richard Aschbacher, Alexander Indra, Christian J Wiedermann, Albert March, Bruno Giacon, Peter Mian, Mirella Bombonato, Angelika Kaneppele, Stefano Sansone, Johanna Burth, Alessandro Felici, Franziska Ebner, Werner Passler, Renelda M Lerchner, Claudio Vedovelli, Greta Spoladore, Raffaella Binazzi, Leonardo Pagani, Ludwig Moroder, Clara Larcher, Elisabetta Pagani
Toxigenic Clostridium difficile is responsible for antibiotic-associated diarrhoea and other diseases. The increasing frequency and severity is attributed to highly-virulent ribotypes such as 027. The aim of the study was to collect epidemiological and molecular data for C. difficile isolates during 2009-2013 in the Central Hospital of Bolzano, Northern Italy. Stool samples from inpatients of the Bolzano Central Hospital were screened for toxins A and B, and C. difficile was cultured and tested for antibiotic susceptibility...
March 1, 2017: Le Infezioni in Medicina
https://www.readbyqxmd.com/read/28349972/enteric-glial-cells-counteract-clostridium-difficile-toxin-b-through-a-nadph-oxidase-ros-jnk-caspase-3-axis-without-involving-mitochondrial-pathways
#12
Lara Macchioni, Magdalena Davidescu, Katia Fettucciari, Maya Petricciuolo, Leonardo Gatticchi, Davide Gioè, Vincenzo Villanacci, Massimo Bellini, Pierfrancesco Marconi, Rita Roberti, Gabrio Bassotti, Lanfranco Corazzi
Enteric glial cells (EGCs) are components of the intestinal epithelial barrier essential for regulating the enteric nervous system. Clostridium difficile is the most common cause of antibiotic-associated colitis, toxin B (TcdB) being the major virulence factor, due to its ability to breach the intestinal epithelial barrier and to act on other cell types. Here we investigated TcdB effects on EGCs and the activated molecular mechanisms. Already at 2 hours, TcdB triggered ROS formation originating from NADPH-oxidase, as demonstrated by their reduction in the presence of the NADPH-oxidase inhibitor ML171...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28349941/milk-fat-globule-membrane-supplementation-in-formula-modulates-the-neonatal-gut-microbiome-and-normalizes-intestinal-development
#13
Ganive Bhinder, Joannie M Allaire, Cyrielle Garcia, Jennifer T Lau, Justin M Chan, Natasha R Ryz, Else S Bosman, Franziska A Graef, Shauna M Crowley, Larissa S Celiberto, Julia C Berkmann, Roger A Dyer, Kevan Jacobson, Michael G Surette, Sheila M Innis, Bruce A Vallance
Breast milk has many beneficial properties and unusual characteristics including a unique fat component, termed milk fat globule membrane (MFGM). While breast milk yields important developmental benefits, there are situations where it is unavailable resulting in a need for formula feeding. Most formulas do not contain MFGM, but derive their lipids from vegetable sources, which differ greatly in size and composition. Here we tested the effects of MFGM supplementation on intestinal development and the microbiome as well as its potential to protect against Clostridium difficile induced colitis...
March 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28348980/overexpression-of-the-endosomal-anion-proton-exchanger-clc-5-increases-cell-susceptibility-toward-clostridium-difficile-toxins-tcda-and-tcdb
#14
Frederike Ruhe, Alexandra Olling, Rasmus Abromeit, Dennis Rataj, Matthias Grieschat, Andre Zeug, Ralf Gerhard, Alexi Alekov
Virulent C. difficile toxins TcdA and TcdB invade host intestinal epithelia by endocytosis and use the acidic environment of intracellular vesicles for further processing and activation. We investigated the role of ClC-5, a chloride/proton exchanger expressed in the endosomes of gastrointestinal epithelial cells, in the activation and processing of C. difficile toxins. Enhanced intoxication by TcdA and TcdB was observed in cells expressing ClC-5 but not ClC-4, another chloride/proton exchanger with similar function but different localization...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28346491/a-genetic-switch-controls-the-production-of-flagella-and-toxins-in-clostridium-difficile
#15
Brandon R Anjuwon-Foster, Rita Tamayo
In the human intestinal pathogen Clostridium difficile, flagella promote adherence to intestinal epithelial cells. Flagellar gene expression also indirectly impacts production of the glucosylating toxins, which are essential to diarrheal disease development. Thus, factors that regulate the expression of the flgB operon will likely impact toxin production in addition to flagellar motility. Here, we report the identification a "flagellar switch" that controls the phase variable production of flagella and glucosylating toxins...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28332133/molecular-typing-and-antimicrobial-susceptibility-testing-to-six-antimicrobials-of-clostridium-difficile-isolates-from-three-czech-hospitals-in-eastern-bohemia-in-2011-2012
#16
V Beran, E J Kuijper, C Harmanus, I M Sanders, S M van Dorp, C W Knetsch, J Janeckova, A Seidelova, L Barekova, J Tvrdik, D Chmelar, I Ciznar
In 2011-2012, a survey was performed in three regional hospitals in the Czech Republic to determine the incidence of Clostridium difficile infections (CDIs) and to characterize bacterial isolates. C. difficile isolates were characterized by PCR ribotyping, toxin genes detection, multiple-locus variable-number tandem-repeat analysis (MLVA), and antimicrobial susceptibility testing to fidaxomicin, vancomycin, metronidazole, clindamycin, LFF571, and moxifloxacin using agar dilution method. The incidence of CDI in three studied hospitals was 145, 146, and 24 cases per 100,000 inhabitants in 2011 and 177, 258, and 67 cases per 100,000 inhabitants in 2012...
March 22, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/28321156/current-knowledge-on-the-laboratory-diagnosis-of-clostridium-difficile-infection
#17
REVIEW
Adrián Martínez-Meléndez, Adrián Camacho-Ortiz, Rayo Morfin-Otero, Héctor Jesús Maldonado-Garza, Licet Villarreal-Treviño, Elvira Garza-González
Clostridium difficile (C. difficile) is a spore-forming, toxin-producing, gram-positive anaerobic bacterium that is the principal etiologic agent of antibiotic-associated diarrhea. Infection with C. difficile (CDI) is characterized by diarrhea in clinical syndromes that vary from self-limited to mild or severe. Since its initial recognition as the causative agent of pseudomembranous colitis, C. difficile has spread around the world. CDI is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28314071/epidemiology-risk-factors-and-outcome-of-clostridium-difficile-infection-in-heart-and-heart-lung-transplant-recipients
#18
Jackrapong Bruminhent, Kelly A Cawcutt, Charat Thongprayoon, Tanya M Petterson, Walter K Kremers, Raymund R Razonable
BACKGROUND: Clostridium difficile is a major cause of diarrhea in thoracic organ transplant recipients. We investigated the epidemiology, risk factors, and outcome of Clostridium difficile infection (CDI) in heart and heart-lung transplant (HT) recipients. METHODS: This is a retrospective study from 2004 to 2013. CDI was defined by diarrhea and a positive toxigenic C. difficile in stool measured by toxin enzyme immunoassay (2004-2006) or polymerase chain reaction (2007-2013)...
March 17, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28301919/clostridium-difficile-toxin-a-induces-reactive-oxygen-species-production-and-p38mapk-activation-to-exert-cellular-toxicity-in-neuronal-cells
#19
Peng Zhang, Ji Hong, I Na Yoon, Jin Ku Kang, Jae Sam Hwang, Ho Kim
Clostridium difficile releases two exotoxins, toxin A and toxin B, which disrupt the epithelial cell barrier in the gut to increase mucosal permeability and trigger inflammation with severe diarrhea. Many studies have suggested that enteric nerves are also directly involved in the progression of this toxin-mediated inflammation and diarrhea. C. difficile toxin A is known to enhance neurotransmitter secretion, increase gut motility, and suppress sympathetic neurotransmission in the guinea pig colitis model. Although previous studies have examined the pathophysiological role of enteric nerves in gut inflammation, the direct effect of toxins on neuronal cells and the molecular mechanisms underlying toxin-induced neuronal stress remained to be unveiled...
March 17, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28286992/cadazolid-for-the-treatment-of-clostridium-difficile
#20
REVIEW
Bradley T Endres, Eugénie Bassères, M Jahangir Alam, Kevin W Garey
Antibiotic development goals for CDI include potent antimicrobial effect against C. difficile, limited killing of host microbiota, potential effect on spores, and ability to interfere with toxin production. Cadazolid, a novel, non-absorbable hybrid antibiotic has many of these criteria. In phase I and II clinical trials, cadazolid was shown to be safe, well tolerated, and efficacious positioning itself as a potential future viable therapeutic option for CDI. Areas covered: This review provides an in-depth evaluation of the chemistry, microbiology, pharmacodynamics, pharmacokinetics, and clinical trial results for cadazolid...
April 2017: Expert Opinion on Investigational Drugs
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