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Clostridium Difficile Toxin

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https://www.readbyqxmd.com/read/28806147/phase-variation-of-clostridium-difficile-virulence-factors
#1
Brandon R Anjuwon-Foster, Rita Tamayo
Clostridium difficile is a leading cause of nosocomial infections, causing disease that ranges from mild diarrhea to potentially fatal colitis. A variety of surface proteins, including flagella, enable C. difficile colonization of the intestine. Once in the intestine, toxigenic C. difficile secretes two glucosylating toxins, TcdA and TcdB, which elicit inflammation and diarrheal disease symptoms. Regulation of colonization factors and TcdA and TcdB is an intense area of research in C. difficile biology. A recent publication from our group describes a novel regulatory mechanism that mediates the ON/OFF expression of co-regulated virulence factors of C...
August 14, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28805376/discovery-and-biosensing-applications-of-diverse-rna-cleaving-dnazymes
#2
Meng Liu, Dingran Chang, Yingfu Li
DNA-based enzymes, or DNAzymes, are not known to exist in Nature but can be isolated from random-sequence DNA pools using test tube selection techniques. Since the report of the first DNAzyme in 1994, many catalytic DNA molecules for catalyzing wide-ranging chemical transformations have been isolated and studied. Our laboratory has a keen interest in searching for diverse DNAzymes capable of cleaving RNA-containing substrates, determining their sequence requirements and structural properties, and examining their potential as biosensors...
August 14, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28805081/bezlotoxumab-for-the-prevention-of-clostridium-difficile-recurrence
#3
Antoine Couture-Cossette, Alex Carignan, Subburaj Ilangumaran, Louis Valiquette
Clostridium difficile infection is a major economic and clinical burden, due to its high frequency of recurrence. Currently recommended treatments are not efficient for prevention and may contribute to the risk of recurrent infection. In recent years, research has focused on strategies to lessen this risk. Bezlotoxumab is a monoclonal antibody that prevents recurrences of C. difficile infection through the antagonism of toxin B. Areas covered: In this review, the authors discuss the burden of C. difficile infection and its recurrences, the mechanisms underlying the recurrences, and current C...
August 13, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28801865/faecal-lactoferrin-and-calprotectin-in-patients-with-clostridium-difficile-infection-a-case-control-study
#4
F Barbut, C Gouot, N Lapidus, L Suzon, R Syed-Zaidi, V Lalande, C Eckert
Calprotectin and lactoferrin are released by the gastrointestinal tract in response to infection and mucosal inflammation. Our objective was to assess the usefulness of quantifying faecal lactoferrin and calprotectin concentrations in Clostridium difficile infection (CDI) patients with or without free toxins in the stools. We conducted a single-centre 22-month case-control study. Patients with a positive CDI diagnosis were compared to two control groups: group 1 = diarrhoeic patients negative for C. difficile and matched (1:1) to CDI cases on the ward location and age, and group 2 = diarrhoeic patients colonised with a non-toxigenic strain of C...
August 12, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28800896/antimicrobial-susceptibility-of-clostridium-difficile-isolates-from-icu-colonized-patients-revealed-alert-to-st-37-rt-017-isolates
#5
Jingyu Yang, Xiaoxia Zhang, Xiaohua Liu, Lin Cai, Ping Feng, Xiaohui Wang, Zhiyong Zong
Seventy Clostridium difficile isolates from ICU colonized patients were tested for antimicrobial susceptibility and screened for resistance determinants. We found that multilocus sequence type 37 (ribotype 017) toxin A-negative/B-positive isolates were more likely resistant to moxifloxacin than toxin A-positive/B-positive isolates (41.7% versus 9.3%) with major variations in both GyrA (Thr82Ile) and GyrB (Ser366Ala), suggesting that the use of quinolone should be more strictly regulated.
July 1, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28800598/an-in-silico-evaluation-of-treatment-regimens-for-recurrent-clostridium-difficile-infection
#6
Natalia Blanco, Betsy Foxman, Anurag N Malani, Min Zhang, Seth Walk, Alexander H Rickard, Marisa C Eisenberg
BACKGROUND: Clostridium difficile infection (CDI) is a significant nosocomial infection worldwide, that recurs in as many as 35% of infections. Risk of CDI recurrence varies by ribotype, which also vary in sporulation and germination rates. Whether sporulation/germination mediate risk of recurrence and effectiveness of treatment of recurring CDI remains unclear. We aim to assess the role of sporulation/germination patterns on risk of recurrence, and the relative effectiveness of the recommended tapered/pulsing regimens using an in silico model...
2017: PloS One
https://www.readbyqxmd.com/read/28794800/genome-characterization-of-a-novel-binary-toxin-positive-strain-of-clostridium-difficile-and-comparison-with-the-epidemic-027-and-078-strains
#7
Zhong Peng, Sidi Liu, Xiujuan Meng, Wan Liang, Zhuofei Xu, Biao Tang, Yuanguo Wang, Juping Duan, Chenchao Fu, Bin Wu, Anhua Wu, Chunhui Li
BACKGROUND: Clostridium difficile is an anaerobic Gram-positive spore-forming gut pathogen that causes antibiotic-associated diarrhea worldwide. A small number of C. difficile strains express the binary toxin (CDT), which is generally found in C. difficile 027 (ST1) and/or 078 (ST11) in clinic. However, we isolated a binary toxin-positive non-027, non-078 C. difficile LC693 that is associated with severe diarrhea in China. The genotype of this strain was determined as ST201. To understand the pathogenesis-basis of C...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/28791215/clostridium-difficile-infections-in-young-infants-case-presentations-and-literature-review
#8
Gé-Ann Kuiper, Joffrey van Prehn, Wim Ang, Frank Kneepkens, Sophie van der Schoor, Tim de Meij
It has been assumed that symptomatic Clostridium difficile infections do not occur in young infants, as this specific group would lack specific C. difficile toxin receptors. As a consequence, it is often current practice not to test for C. difficile in neonates and young infants up to 2 years of age presenting with (bloody) diarrhea. The evidence to support this is, however, weak and largely based on small, poorly designed animal studies. We present two young infants with recurrent bloody diarrhea following antimicrobial therapy, positive testing for toxigenic C...
2017: IDCases
https://www.readbyqxmd.com/read/28790999/immunization-with-recombinant-tcdb-encapsulated-nanocomplex-induces-protection-against-clostridium-difficile-challenge-in-a-mouse-model
#9
Yi-Wen Liu, Yu-Hung Chen, Jenn-Wei Chen, Pei-Jane Tsai, I-Hsiu Huang
Clostridium difficile is considered to be one of the major cause of infectious diarrhea in healthcare systems worldwide. Symptoms of C. difficile infection are caused largely by the production of two cytotoxins: toxin A (TcdA) and toxin B (TcdB). Vaccine development is considered desirable as it would decrease the mounting medical costs and mortality associated with C. difficile infections. Biodegradable nanoparticles composed of poly-γ-glutamic acid (γ-PGA) and chitosan have proven to be a safe and effective antigen delivery system for many viral vaccines...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28790208/pathogenicity-locus-core-genome-and-accessory-gene-contributions-to-clostridium-difficile-virulence
#10
Brittany B Lewis, Rebecca A Carter, Lilan Ling, Ingrid Leiner, Ying Taur, Mini Kamboj, Erik R Dubberke, Joao Xavier, Eric G Pamer
Clostridium difficile is a spore-forming anaerobic bacterium that causes colitis in patients with disrupted colonic microbiota. While some individuals are asymptomatic C. difficile carriers, symptomatic disease ranges from mild diarrhea to potentially lethal toxic megacolon. The wide disease spectrum has been attributed to the infected host's age, underlying diseases, immune status, and microbiome composition. However, strain-specific differences in C. difficile virulence have also been implicated in determining colitis severity...
August 8, 2017: MBio
https://www.readbyqxmd.com/read/28780742/is-there-a-relationship-between-the-presence-of-the-binary-toxin-genes-in-clostridium-difficile-strains-and-the-severity-of-c-difficile-infection-cdi
#11
C E Berry, K A Davies, D W Owens, M H Wilcox
Some strains of Clostridium difficile produce a binary toxin, in addition to the main C. difficile virulence factors (toxins A and B). There have been conflicting reports regarding the role of binary toxin and its relationship to the severity of C. difficile infection (CDI). Samples, isolates and clinical data were collected as part of a prospective multicentre diagnostic study. Clostridium difficile isolates (n = 1259) were tested by polymerase chain reaction (PCR) assay to detect binary toxin genes cdtA and cdtB...
August 5, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28776206/healthcare-associated-clostridium-difficile-infections-are-sustained-by-disease-from-the-community
#12
Angus McLure, Archie C A Clements, Martyn Kirk, Kathryn Glass
Clostridium difficile infections (CDIs) are some of the most common hospital-associated infections worldwide. Approximately 5% of the general population is colonised with the pathogen, but most are protected from disease by normal intestinal flora or immune responses to toxins. We developed a stochastic compartmental model of CDI in hospitals that captures the condition of the host's gut flora and the role of adaptive immune responses. A novel, derivative-based method for sensitivity analysis of individual-level outcomes was developed and applied to the model...
August 3, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28776043/amino-acid-differences-in-the-1753-to-1851-region-of-tcdb-influence-variations-in-tcdb1-and-tcdb2-cell-entry
#13
Jonathan J Hunt, Jason L Larabee, Jimmy D Ballard
Clostridium difficile TcdB2 enters cells with a higher efficiency than TcdB1 and exhibits an overall higher level of toxicity. However, the TcdB2-specific sequences that account for more efficient cell entry have not been reported. In this study, we examined the contribution of carboxy-terminal sequence differences to TcdB activity by comparing the binding, uptake, and endosomal localization of TcdB1 and TcdB2 or selected recombinant fragments of these proteins. Our findings suggest that sequence differences in the amino acid 1753 to 1851 region proximal to the combined repetitive oligopeptide domain (CROP) support enhanced uptake of TcdB2 and localization of toxin in acidified endosomes...
July 2017: MSphere
https://www.readbyqxmd.com/read/28765714/high-prevalence-of-subclass-specific-binding-and-neutralizing-antibodies-against-clostridium-difficile-toxins-in-adult-cystic-fibrosis-sera-possible-mode-of-immunoprotection-against-symptomatic-c-difficile-infection
#14
Tanya M Monaghan, Ola H Negm, Brendon MacKenzie, Mohamed R Hamed, Clifford C Shone, David P Humphreys, K Ravi Acharya, Mark H Wilcox
OBJECTIVES: Despite multiple risk factors and a high rate of colonization for Clostridium difficile, the occurrence of C. difficile infection in patients with cystic fibrosis is rare. The aim of this study was to compare the prevalence of binding C. difficile toxin-specific immunoglobulin (Ig)A, IgG and anti-toxin neutralizing antibodies in the sera of adults with cystic fibrosis, symptomatic C. difficile infection (without cystic fibrosis) and healthy controls. METHODS: Subclass-specific IgA and IgG responses to highly purified whole C...
2017: Clinical and Experimental Gastroenterology
https://www.readbyqxmd.com/read/28764997/effects-of-clostridium-perfringens-iota-toxin-in-the-small-intestine-of-mice
#15
Leandro M Redondo, Enzo A Redondo, Gabriela C Dailoff, Carlos L Leiva, Juan M Díaz-Carrasco, Octavio A Bruzzone, Adriana Cangelosi, Patricia Geoghegan, Mariano E Fernandez-Miyakawa
Iota toxin is a binary toxin solely produced by Clostridium perfringens type E strains, and is structurally related to CDT from C. difficile and CST from C. spiroforme. As type E causes hemorrhagic enteritis in cattle, it is usually assumed that associated diseases are mediated by iota toxin, although evidence in this regard has not been provided. In the present report, iota toxin intestinal effects were evaluated in vivo using a mouse model. Histological damage was observed in ileal loops treated with purified iota toxin after 4 h of incubation...
July 29, 2017: Anaerobe
https://www.readbyqxmd.com/read/28764868/modeling-new-immunoregulatory-therapeutics-as-antimicrobial-alternatives-for-treating-clostridium-difficile-infection
#16
Andrew Leber, Raquel Hontecillas, Vida Abedi, Nuria Tubau-Juni, Victoria Zoccoli-Rodriguez, Caroline Stewart, Josep Bassaganya-Riera
The current treatment paradigm in Clostridium difficile infection is the administration of antibiotics contributing to the high rates of recurrent infections. Recent alternative strategies, such as fecal microbiome transplantation and anti-toxin antibodies, have shown similar efficacy in the treatment of C. difficile associated disease (CDAD). However, barriers exist for either treatment or other novel treatments to displace antibiotics as the standard of care. To aid in the comparison of these and future treatments in CDAD, we developed an in silico pipeline to predict clinical efficacy with nonclinical results...
May 2017: Artificial Intelligence in Medicine
https://www.readbyqxmd.com/read/28761936/clostridium-difficile-colonizes-alternative-nutrient-niches-during-infection-across-distinct-murine-gut-microbiomes
#17
Matthew L Jenior, Jhansi L Leslie, Vincent B Young, Patrick D Schloss
Clostridium difficile is the largest single cause of hospital-acquired infection in the United States. A major risk factor for Clostridium difficile infection (CDI) is prior exposure to antibiotics, as they disrupt the gut bacterial community which protects from C. difficile colonization. Multiple antibiotic classes have been associated with CDI susceptibility, many leading to distinct community structures stemming from variation in bacterial targets of action. These community structures present separate metabolic challenges to C...
July 2017: MSystems
https://www.readbyqxmd.com/read/28760168/the-impact-of-a-computerized-clinical-decision-support-tool-on-inappropriate-clostridium-difficile-testing
#18
Duncan R White, Keith W Hamilton, David A Pegues, Asaf Hanish, Craig A Umscheid
OBJECTIVE To evaluate the effectiveness of a computerized clinical decision support intervention aimed at reducing inappropriate Clostridium difficile testing DESIGN Retrospective cohort study SETTING University of Pennsylvania Health System, comprised of 3 large tertiary-care hospitals PATIENTS All adult patients admitted over a 2-year period INTERVENTION Providers were required to use an order set integrated into a commercial electronic health record to order C. difficile toxin testing. The order set identified patients who had received laxatives within the previous 36 hours and displayed a message asking providers to consider stopping laxatives and reassessing in 24 hours prior to ordering C...
August 1, 2017: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/28759258/nonantimicrobial-drug-targets-for-clostridium-difficile-infections
#19
Charles Darkoh, Magdalena Deaton, Herbert L DuPont
Clostridium difficile infection (CDI) is a major public health problem worldwide. Treatment has become complicated due to the emergence of strains with increased toxigenicity and sporulation rate, together with rampant antibiotics use that disrupts colonization resistance of the colonic microbiota. As a result, there is a critical need for nonantibiotic treatments. Therapies based on inhibiting the toxins, bacterial structures responsible for colonization, virulence and restoration of the gut microbiota are the most important nonantibiotic targets to combat CDI...
July 31, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28751156/performance-evaluation-of-the-verigene-%C3%A2-clostridium-difficile-nucleic-acid-test-an-automated-multiplex-molecular-testing-system-for-detection-of-c-%C3%A2-difficile-toxin
#20
Kosuke Kosai, Yuki Iwanaga, Norihiko Akamatsu, Yuya Okada, Norihito Kaku, Naoki Uno, Yoshitomo Morinaga, Hiroo Hasegawa, Taiga Miyazaki, Koichi Izumikawa, Hiroshi Mukae, Katsunori Yanagihara
The Verigene(®)Clostridium difficile nucleic acid test (Verigene(®) CDF test) is an automatic and rapid detection system for the genes encoding tcdA, tcdB, binary toxin, and the single nucleotide deletion at base pair 117 in the tcdC based on microarray and PCR amplification. We compared the performance of the Verigene(®) CDF test to that of two enzyme immunoassays, C. DIFF QUIK CHEK COMPLETE and X/Pect Toxin A/B, using 118 specimens. We found overall concordance rates of 81.4% and 78.8% between C. DIFF QUIK CHEK COMPLETE and Verigene(®) CDF test, and X/Pect Toxin A/B and Verigene(®) CDF test...
July 24, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
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