Pseudomembranous colitis caused by toxin A-negative/toxin B-positive variant strain of Clostridium difficile

Toyokawa, Masahiro; Ueda, Akiko; H, Tsukamoto; Nishi, Isao; Horikawa, Masayuki; Sunada, Atsuko; Asari, Seishi

doi:10.1007/s10156-003-0269-z

Cited by 13 publications

(11 citation statements)

References 8 publications

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“…However, several reports have described the detection of A−/B+ strains in fecal specimens submitted in Japanese hospitals. 3,9,[12][13][14][15][16] Therefore, in the present patient, we speculate that the A−/B+ strain isolated from the abdominal surgical wound originated from inside the patient's colon and contaminated the surgical site during or after the abdominal operation. The fact that C. diffi cile was detected in a toxin A-negative fecal specimen submitted on day 36 may support our speculation.…”

Section: Discussionmentioning

confidence: 99%

Surgical-site infection with toxin A-nonproducing and toxin B-producing Clostridium difficile

Kikkawa

Miyamoto

Takiguchi

et al. 2008

Journal of Infection and Chemotherapy

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Section: Discussionmentioning

confidence: 99%

Surgical-site infection with toxin A-nonproducing and toxin B-producing Clostridium difficile

Kikkawa

Miyamoto

Takiguchi

et al. 2008

Journal of Infection and Chemotherapy

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Section: Introductionmentioning

confidence: 99%

“…Until recently, it was presumed that a strain must produce both toxins to be considered fully pathogenic. However, it is still unclear (i) why strains that do not produce toxin A (A2B+ variant strains) are yet responsible for diarrhoea and even PMC (Alfa et al, 2000;Toyokawa et al, 2003), and (ii) why some patients infected by toxinogenic strains will present a mild diarrhoea, whereas others will present a fulminant PMC.Abbreviations: AAD, antibiotic-associated diarrhoea; MLST, multilocus sequence typing; PaLoc, pathogenicity locus; PMC, pseudomembranous colitis; ST, sequence type; UPGMA, unweighted pairgroup method with arithmetic means.Nucleotide sequences of the internal fragment genes analysed in this work will be deposited in GenBank under accession numbers DQ102375-DQ102379 (for cdtA), DQ117049-DQ117053 (for cdtB), DQ117054-DQ117074 (for cwp66), DQ117075-DQ117103 (for cwp84), DQ117104-DQ117132 (for fbp68), DQ117133-DQ117161 (for fliC), DQ117162-DQ117189 (for fliD), DQ117190-DQ117218 (for groEL), DQ117219-DQ117240 (for slpA), DQ117241-DQ117265 (for tcdA), DQ117266-DQ117288 (for tcdB) and DQ117289-DQ117311 (for tcdD). Differences in the levels of production of toxins A and B cannot alone account for the wide spectrum of clinical presentations.…”

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confidence: 99%

Multilocus sequence analysis and comparative evolution of virulence-associated genes and housekeeping genes of Clostridium difficile

et al. 2005

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A multilocus sequence analysis of ten virulence-associated genes was performed to study the genetic relationships between 29 Clostridium difficile isolates of various origins, hosts and clinical presentations, and selected from the main lineages previously defined by multilocus sequence typing (MLST) of housekeeping genes. Colonization-factor-encoding genes (cwp66, cwp84, fbp68, fliC, fliD, groEL and slpA), toxin A and B genes (tcdA and tcdB), and the toxin A and B positive regulator gene (tcdD) were investigated. Binary toxin genes (cdtA and cdtB) were also detected, and internal fragments were sequenced for positive isolates. Virulence-associated genes exhibited a moderate polymorphism, comparable to the polymorphism of housekeeping genes, whereas cwp66 and slpA genes appeared highly polymorphic. Isolates recovered from human pseudomembranous colitis cases did not define a specific lineage. The presence of binary toxin genes, detected in five of the 29 isolates (17 %), was also not linked to clinical presentation. Conversely, toxigenic A"B+ isolates defined a very homogeneous lineage, which is distantly related to other isolates. By clustering analysis, animal isolates were intermixed with human isolates. Multilocus sequence analysis of virulence-associated genes is consistent with a clonal population structure for C. difficile and with the lack of host specificity. The data suggest a co-evolution of several of the virulence-associated genes studied (including toxins A and B and the binary toxin genes) with housekeeping genes, reflecting the genetic background of C. difficile, whereas flagellin, cwp66 and slpA genes may undergo recombination events and/or environmental selective pressure. INTRODUCTIONSince its recognition as the main cause of pseudomembranous colitis (PMC) in 1978, Clostridium difficile has emerged as an important enteropathogen (Bartlett et al., 1978;Johnson & Gerding, 1998;Larson et al., 1978). C. difficile is currently responsible for virtually all cases of PMC and for 10-25 % of antibiotic-associated diarrhoea (AAD) (Bartlett, 1994;Kelly et al., 1994). It is also the leading cause of nosocomial diarrhoea, and many hospital outbreaks have been described throughout the world (Barbut et al., 1994; Cartmill et al., 1994; McEllistrem et al., 2005). The two main virulence factors are exotoxins, toxins A (enterotoxin) and B (cytotoxin), both of which damage the human colonic mucosa and are potent tissue-damaging enzymes (Bongaerts & Lyerly, 1994;Borriello, 1998). Until recently, it was presumed that a strain must produce both toxins to be considered fully pathogenic. However, it is still unclear (i) why strains that do not produce toxin A (A2B+ variant strains) are yet responsible for diarrhoea and even PMC (Alfa et al., 2000;Toyokawa et al., 2003), and (ii) why some patients infected by toxinogenic strains will present a mild diarrhoea, whereas others will present a fulminant PMC.Abbreviations: AAD, antibiotic-associated diarrhoea; MLST, multilocus sequence typing; PaLoc, pathogenicity locus; P...

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“…However, production of these toxins alone cannot explain C. difficile pathogenesis. In recent years, increasing numbers of strains have been reported from several countries with truncated versions of toxin A and/or toxin B (10,31).…”

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Comparative Phylogenomics of Clostridium difficile Reveals Clade Specificity and Microevolution of Hypervirulent Strains

Gerding²,

et al. 2006

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Clostridium difficile is the most frequent cause of nosocomial diarrhea worldwide, and recent reports suggested the emergence of a hypervirulent strain in North America and Europe. In this study, we applied comparative phylogenomics (whole-genome comparisons using DNA microarrays combined with Bayesian phylogenies) to model the phylogeny of C. difficile, including 75 diverse isolates comprising hypervirulent, toxin-variable, and animal strains. The analysis identified four distinct statistically supported clusters comprising a hypervirulent clade, a toxin A ؊ B ؉ clade, and two clades with human and animal isolates. Genetic differences among clades revealed several genetic islands relating to virulence and niche adaptation, including antibiotic resistance, motility, adhesion, and enteric metabolism. Only 19.7% of genes were shared by all strains, confirming that this enteric species readily undergoes genetic exchange. This study has provided insight into the possible origins of C. difficile and its evolution that may have implications in disease control strategies.

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Pseudomembranous colitis caused by toxin A-negative/toxin B-positive variant strain of Clostridium difficile

Cited by 13 publications

References 8 publications

Surgical-site infection with toxin A-nonproducing and toxin B-producing Clostridium difficile

Surgical-site infection with toxin A-nonproducing and toxin B-producing Clostridium difficile

Multilocus sequence analysis and comparative evolution of virulence-associated genes and housekeeping genes of Clostridium difficile

Comparative Phylogenomics of Clostridium difficile Reveals Clade Specificity and Microevolution of Hypervirulent Strains

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