scholarly journals Variant forms of the binary toxin CDT locus and tcdC gene in Clostridium difficile strains

2007 ◽  
Vol 56 (3) ◽  
pp. 329-335 ◽  
Author(s):  
Barbara Geric Stare ◽  
Michel Delmée ◽  
Maja Rupnik
Keyword(s):  
Clostridium Difficile ◽  
Binary Toxin

scholarly journals Characterizations of Clinical Isolates of Clostridium difficile by Toxin Genotypes and by Susceptibility to 12 Antimicrobial Agents, Including Fidaxomicin (OPT-80) and Rifaximin: a Multicenter Study in Taiwan

2012 ◽  
Vol 56 (7) ◽  
pp. 3943-3949 ◽  
Author(s):  
Chun-Hsing Liao ◽  
Wen-Chien Ko ◽  
Jang-Jih Lu ◽  
Po-Ren Hsueh
Keyword(s):  
Clostridium Difficile ◽  
Care Setting ◽  
Antimicrobial Agents ◽  
Teaching Hospitals ◽  
Binary Toxin ◽  
Content Type ◽  
Vancomycin Mics ◽  
Major Teaching ◽  
Southern Taiwan

ABSTRACTA total of 403 nonduplicate isolates ofClostridium difficilewere collected at three major teaching hospitals representing northern, central, and southern Taiwan from January 2005 to December 2010. Of these 403 isolates, 170 (42.2%) were presumed to be nontoxigenic due to the absence of genes for toxins A or B or binary toxin. The remaining 233 (57.8%) isolates carried toxin A and B genes, and 39 (16.7%) of these also had binary toxin genes. The MIC90of all isolates for fidaxomicin and rifaximin was 0.5 μg/ml (range, ≤0.015 to 0.5 μg/ml) and >128 μg/ml (range, ≤0.015 to >128 μg/ml), respectively. All isolates were susceptible to metronidazole (MIC90of 0.5 μg/ml; range, ≤0.03 to 4 μg/ml). Two isolates had reduced susceptibility to vancomycin (MICs, 4 μg/ml). Only 13.6% of isolates were susceptible to clindamycin (MIC of ≤2 μg/ml). Nonsusceptibility to moxifloxacin (n= 81, 20.1%) was accompanied by single or multiple mutations ingyrAandgyrBgenes in all but eight moxifloxacin-nonsusceptible isolates. Two previously unreportedgyrBmutations might independently confer resistance (MIC, 16 μg/ml), Ser416 to Ala and Glu466 to Lys. Moxifloxacin-resistant isolates were cross-resistant to ciprofloxacin and levofloxacin, but some moxifloxacin-nonsusceptible isolates remained susceptible to gemifloxacin or nemonoxacin at 0.5 μg/ml. This study found the diversity of toxigenic and nontoxigenic strains ofC. difficilein the health care setting in Taiwan. All isolates tested were susceptible to metronidazole and vancomycin. Fidaxomicin exhibited potentin vitroactivity against all isolates tested, while the more than 10% of Taiwanese isolates with rifaximin MICs of ≥128 μg/ml raises concerns.

Molecular characterization and antimicrobial susceptibility patterns of Clostridium difficile strains isolated from hospitals in south-east Scotland

2007 ◽  
Vol 56 (7) ◽  
pp. 921-929 ◽  
Author(s):  
Esvet Mutlu ◽  
Allison J. Wroe ◽  
Karla Sanchez-Hurtado ◽  
Jon S. Brazier ◽  
Ian R. Poxton
Keyword(s):  
Antibiotic Resistance ◽  
Clostridium Difficile ◽  
Restriction Analysis ◽  
Common Type ◽  
Resistance Pattern ◽  
Binary Toxin ◽  
Resistance Patterns ◽  
The Common ◽  
Antibiotic Resistance Patterns ◽  
Susceptibility Patterns

Clostridium difficile isolates (n=149) collected in south-east Scotland between August and October 2005 were typed by four different methods and their susceptibility to seven different antibiotics was determined. The aims were to define the types of strain occurring in this region and to determine whether there were any clonal relationships among them with respect to genotype and antibiotic resistance pattern. Ribotyping revealed that 001 was the most common type (n=113, 75.8 %), followed by ribotype 106 (12 isolates, 8.1 %). The majority of the isolates (96.6 %, n=144) were of toxinotype 0, with two toxinotype V isolates and single isolates of toxinotypes I, IV and XIII. PCR and restriction analysis of the fliC gene from 147 isolates gave two restriction patterns: 145 of pattern VII and two of pattern I. Binary toxin genes were detected in only three isolates: two isolates of ribotype 126, toxinotype V, and one isolate of ribotype 023, toxinotype IV. S-types showed more variation, with 64.5 % (n=40) of the common S-type (4939) and 21 % (n=13) of S-type 4741, with six other S-types (one to three isolates each). All ribotype 001 isolates were of the same S-type (4939), with three isolates of other ribotypes being this S-type. No resistance was found to metronidazole or vancomycin, with resistance to tetracycline only found in 4.3 % of the isolates. A high proportion of isolates were resistant to clindamycin (62.9 %), moxifloxacin, ceftriaxone (both 87.1 %) and erythromycin (94.8 %). Resistance to three antibiotics (erythromycin, clindamycin and ceftriaxone) was seen in 66 isolates, with erythromycin, ceftriaxone and moxifloxacin resistance seen in 96 isolates. Resistance to all four of these antibiotics was found in 62 isolates and resistance to five (the above plus tetracycline) in one isolate: a ribotype 001, toxinotype 0 strain. Whilst ribotype 001 was the most commonly encountered type, there was no evidence of clonal relationships when all other typing and antibiotic resistance patterns were taken into account.

scholarly journals Evaluation of the Cepheid Xpert C. difficile/Epiand Meridian Bioscienceillumigene C. difficile Assays for Detecting Clostridium difficile Ribotype 033 Strains

2014 ◽  
Vol 53 (3) ◽  
pp. 973-975 ◽  
Author(s):  
Grace O. Androga ◽  
Alan M. McGovern ◽  
Briony Elliott ◽  
Barbara J. Chang ◽  
Timothy T. Perkins ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Binary Toxin ◽  
Content Type ◽  
Toxin Genes ◽  
Production Animals

Clostridium difficilePCR ribotype 033 (RT033) is found in the gastrointestinal tracts of production animals and, occasionally, humans. TheillumigeneC. difficileassay (Meridian Bioscience, Inc.) failed to detect any of 52C. difficileRT033 isolates, while all strains signaled positive for the binary toxin genes but were reported as negative forC. difficileby the XpertC. difficile/Epiassay (Cepheid).

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.

scholarly journals Frequency of Binary Toxin Genes among Clostridium difficile Strains That Do Not Produce Large Clostridial Toxins

2003 ◽  
Vol 41 (11) ◽  
pp. 5227-5232 ◽  
Author(s):  
B. Geric ◽  
S. Johnson ◽  
D. N. Gerding ◽  
M. Grabnar ◽  
M. Rupnik
Keyword(s):  
Clostridium Difficile ◽  
Binary Toxin ◽  
Toxin Genes

scholarly journals 1H, 13C, and 15N resonance assignments of an enzymatically active domain from the catalytic component (CDTa, residues 216–420) of a binary toxin from Clostridium difficile

2016 ◽  
Vol 10 (1) ◽  
pp. 213-217 ◽  
Author(s):  
Braden M. Roth ◽  
Raquel Godoy-Ruiz ◽  
Kristen M. Varney ◽  
Richard R. Rustandi ◽  
David J. Weber
Keyword(s):  
Clostridium Difficile ◽  
Resonance Assignments ◽  
Binary Toxin

scholarly journals Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages

2016 ◽  
Vol 55 (3) ◽  
pp. 865-876 ◽  
Author(s):  
M. D. Cairns ◽  
M. D. Preston ◽  
C. L. Hall ◽  
D. N. Gerding ◽  
P. M. Hawkey ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Antibiotic Resistance Genes ◽  
Binary Toxin ◽  
Human Origins ◽  
Comparative Genome Analysis ◽  
Toxin B ◽  
Content Type ◽  
Global Spread ◽  
Animal Isolates ◽  
Evolutionary Lineages

ABSTRACT The diarrheal pathogen Clostridium difficile consists of at least six distinct evolutionary lineages. The RT017 lineage is anomalous, as strains only express toxin B, compared to strains from other lineages that produce toxins A and B and, occasionally, binary toxin. Historically, RT017 initially was reported in Asia but now has been reported worldwide. We used whole-genome sequencing and phylogenetic analysis to investigate the patterns of global spread and population structure of 277 RT017 isolates from animal and human origins from six continents, isolated between 1990 and 2013. We reveal two distinct evenly split sublineages (SL1 and SL2) of C. difficile RT017 that contain multiple independent clonal expansions. All 24 animal isolates were contained within SL1 along with human isolates, suggesting potential transmission between animals and humans. Genetic analyses revealed an overrepresentation of antibiotic resistance genes. Phylogeographic analyses show a North American origin for RT017, as has been found for the recently emerged epidemic RT027 lineage. Despite having only one toxin, RT017 strains have evolved in parallel from at least two independent sources and can readily transmit between continents.

scholarly journals Structure of the cell-binding component of the Clostridium difficile binary toxin reveals a di-heptamer macromolecular assembly

2020 ◽  
Vol 117 (2) ◽  
pp. 1049-1058 ◽  
Author(s):  
Xingjian Xu ◽  
Raquel Godoy-Ruiz ◽  
Kaylin A. Adipietro ◽  
Christopher Peralta ◽  
Danya Ben-Hail ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Receptor Binding ◽  
Treatment Options ◽  
Binding Domain ◽  
Binary Toxin ◽  
Receptor Binding Domain ◽  
Design Strategies ◽  
Recurrence Rates ◽  
Structure Based Drug Design ◽  
Starting Point

Targeting Clostridium difficile infection is challenging because treatment options are limited, and high recurrence rates are common. One reason for this is that hypervirulent C. difficile strains often have a binary toxin termed the C. difficile toxin, in addition to the enterotoxins TsdA and TsdB. The C. difficile toxin has an enzymatic component, termed CDTa, and a pore-forming or delivery subunit termed CDTb. CDTb was characterized here using a combination of single-particle cryoelectron microscopy, X-ray crystallography, NMR, and other biophysical methods. In the absence of CDTa, 2 di-heptamer structures for activated CDTb (1.0 MDa) were solved at atomic resolution, including a symmetric (SymCDTb; 3.14 Å) and an asymmetric form (AsymCDTb; 2.84 Å). Roles played by 2 receptor-binding domains of activated CDTb were of particular interest since the receptor-binding domain 1 lacks sequence homology to any other known toxin, and the receptor-binding domain 2 is completely absent in other well-studied heptameric toxins (i.e., anthrax). For AsymCDTb, a Ca2+ binding site was discovered in the first receptor-binding domain that is important for its stability, and the second receptor-binding domain was found to be critical for host cell toxicity and the di-heptamer fold for both forms of activated CDTb. Together, these studies represent a starting point for developing structure-based drug-design strategies to target the most severe strains of C. difficile.

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