Clostridium difficile: clinical disease and diagnosis

Knoop, Floyd C.; Owens, M.J.; Crocker, I.C.

doi:10.1128/cmr.6.3.251

Cited by 149 publications

(111 citation statements)

References 250 publications

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“…On the basis of F o Ϫ F c electron density, side chain atoms were omitted at some positions. Water molecules were added at positions where F o Ϫ F c electron density peaks exceeded 3 and potential hydrogen bonds could be made. Detailed refinement statistics for all of the structures are given in Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…Strains of C. difficile produce a variety of virulence factors, notable among which are several protein toxins: Toxin A, Toxin B (4 -6), and, in some strains, the binary toxin CDT, 3 which is similar to Clostridium perfringens iota toxin and Clostridium botulinum C2 toxin (7)(8)(9). Toxins A and B are large protein cytotoxins that play a key role in the pathology of infection and most probably are involved in the gut colonization process.…”

mentioning

confidence: 99%

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Structural Basis for Substrate Recognition in the Enzymatic Component of ADP-ribosyltransferase Toxin CDTa from Clostridium difficile

Sundriyal

Roberts²,

Shone³

et al. 2009

Journal of Biological Chemistry

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ADP-ribosylation is one of the favored modes of cell intoxication employed by several bacteria. Clostridium difficile is recognized to be an important nosocomial pathogen associated with considerable morbidity and attributable mortality. Along with its two well known toxins, Toxin A and Toxin B, it produces an ADP-ribosylating toxin that targets monomeric actin of the target cell. Like other Clostridial actin ADP-ribosylating toxins, this binary toxin, known as C. difficile toxin (CDT), is composed of two subunits, CDTa and CDTb. In this study, we present high resolution crystal structures of CDTa in its native form (at pH 4.0, 8.5, and 9.0) and in complex with ADP-ribose donors, NAD and NADPH (at pH 9.0). The crystal structures of the native protein show "pronounced conformational flexibility" confined to the active site region of the protein and "enhanced" disorder at low pH, whereas the complex structures highlight significant differences in "ligand specificity" compared with the enzymatic subunit of a close homologue, Clostridium perfringens iota toxin. Specifically in CDTa, two of the suggested catalytically important residues (Glu-385 and Glu-387) seem to play no role or a less important role in ligand binding. These structural data provide the first detailed information on protein-donor substrate complex stabilization in CDTa, which may have implications in understanding CDT recognition.Clostridium difficile infection is a major problem as a healthcare-associated infection. The bacterium causes nosocomial, antibiotic-associated diarrhea and pseudomembranous colitis in patients treated with broad spectrum antibiotics (1-3). Elderly patients are most at risk from these potentially life-threatening diseases, and incidents of hospital infection have increased dramatically over the last 10 years.Strains of C. difficile produce a variety of virulence factors, notable among which are several protein toxins: Toxin A, Toxin B (4 -6), and, in some strains, the binary toxin CDT, 3 which is similar to Clostridium perfringens iota toxin and Clostridium botulinum C2 toxin (7-9). Toxins A and B are large protein cytotoxins that play a key role in the pathology of infection and most probably are involved in the gut colonization process. Outbreaks of C. difficile infection have been reported with Toxin A-negative/Toxin B-positive strains, and a recent report (10) suggests that Toxin B plays a major role in the disease pathology. Little is presently known about the contribution of the binary toxin to C. difficile infection.CDT binary toxin belongs to the family of actin-specific ADP-ribosylating toxin (ADPRT) (for a recent review see Ref.11), composed of two independently produced components: a transport component of 99 kDa (CDTb) that facilitates translocation of the enzymatic component of 49 kDa (CDTa) into the target cell that is capable of transferring ADP-ribose group of NAD/NADPH to monomeric actin molecules in target cells (9,12,13). This irreversible modification of G-actin at 14) blocks its polymerization and thus...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Structural Basis for Substrate Recognition in the Enzymatic Component of ADP-ribosyltransferase Toxin CDTa from Clostridium difficile

Sundriyal

Roberts²,

Shone³

et al. 2009

Journal of Biological Chemistry

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“…The present study was carried out during April to toxic megacolon, which can be life-threatening and 2008-January 2010 in the Department of Food may lead to colonic perforation, sepsis and even death Hygiene, Faculty of Veterinary Medicine, Assiut [3,4]. University, Assiut, Egypt.…”

Section: Methodsmentioning

confidence: 99%

Detection of toxigenic Clostridium difficile in powdered infant and follow-up formulae in Egypt

Saad¹,

Amin²,

Shaker³

2013

Vet World

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Aim: To examine powdered infant formula (PIF) and follow-up formula (FUF) for the presence of toxigenic Clostridium difficile. Materials and Methods:A total of 100 random samples of PIF and FUF, 50 samples each, from various pharmacies and supermarkets located in Assiut city were collected during 2008-2010. Results:Our results show that 16 out of 100 (16%) examined samples of PIF and FUF were contaminated with C. difficile; 4 (8%) and 12 (24%) of the examined PIF and FUF samples tested positive for C. difficile, respectively. Only two (16.67%) isolates of C. difficile from the examined FUF were toxigenic, while the isolates from the PIF samples were not toxigenic. Conclusions:The presence of C. difficile in PIF and FUF samples suggests that there is a high potential for the transmission of C. difficile through these products. Thus, proper preparation and handling of these products is required to reduce the risk of the illnesses arising due to C. difficile.

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“…The symptoms range from a mild disturbance to severe illness with ulceration and bleeding from the colon and perforation of the intestine, which can be fatal (Bartlett 1990;Knoop et al 1993). Patients treated with broad spectrum antibiotics are at the greatest risk of contracting C. difficile infection.…”

Section: Introductionmentioning

confidence: 99%

Metabolite profiling of Clostridium difficile ribotypes using small molecular weight volatile organic compounds

Kuppusami

Clokie²,

Panayi³

et al. 2014

Metabolomics

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Clostridium difficile: clinical disease and diagnosis

Cited by 149 publications

References 250 publications

Structural Basis for Substrate Recognition in the Enzymatic Component of ADP-ribosyltransferase Toxin CDTa from Clostridium difficile

Structural Basis for Substrate Recognition in the Enzymatic Component of ADP-ribosyltransferase Toxin CDTa from Clostridium difficile

Detection of toxigenic Clostridium difficile in powdered infant and follow-up formulae in Egypt

Metabolite profiling of Clostridium difficile ribotypes using small molecular weight volatile organic compounds

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