Binary toxin locus analysis in Clostridium difficile

Metcalf, Devon; Weese, J. Scott

doi:10.1099/jmm.0.028498-0

Cited by 19 publications

(17 citation statements)

References 27 publications

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“…The cognate sensor histidine kinase that interacts with the orphan histidine kinase CdtR has yet to be identified 139 . A truncation in the C. difficile PCR ribotype 078 CdtR does not abrogate CDT expression, suggesting that full-length CdtR is not essential for expression 140 . In contrast to the PaLoc, the environmental signals that regulate the expression of the CdtLoc genes are not known.…”

Section: Mechanisms/pathophysiologymentioning

confidence: 98%

Clostridium difficile infection

Smits

Lyras

Lacy

et al. 2016

Nat Rev Dis Primers

660

674

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Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis — the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota.

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Section: Mechanisms/pathophysiologymentioning

confidence: 98%

Clostridium difficile infection

Smits

Lyras

Lacy

et al. 2016

Nat Rev Dis Primers

660

674

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“…ACCEPTED MANUSCRIPT 14 inhibition of 86 Rb + release [91]. PA uses a similar mechanism to translocate the enzymatic components (EF, LF) into the cytosol [112,113].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Pore-forming activity of clostridial binary toxins

Knapp

Benz

Popoff

2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Clostridial binary toxins (Clostridium perfringens Iota toxin, Clostridium difficile transferase, Clostridium spiroforme toxin, Clostridium botulinum C2 toxin) as Bacillus binary toxins, including Bacillus anthracis toxins consist of two independent proteins, one being the binding component which mediates the internalization into cell of the intracellularly active component. Clostridial binary toxins induce actin cytoskeleton disorganization through mono-ADP-ribosylation of globular actin and are responsible for enteric diseases. Clostridial and Bacillus binary toxins share structurally and functionally related binding components which recognize specific cell receptors, oligomerize, form pores in endocytic vesicle membrane, and mediate the transport of the enzymatic component into the cytosol. Binding components retain the global structure of pore-forming toxins (PFTs) from the cholesterol-dependent cytotoxin family such as perfringolysin. However, their pore-forming activity notably that of clostridial binding components is more related to that of heptameric PFT family including aerolysin and C. perfringens epsilon toxin. This review focuses upon pore-forming activity of clostridial binary toxins compared to other related PFTs. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale.

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“…Popoff et al have studied variability in the CDT regulatory gene cdtR and could distinguished five lineages which correlated well with types of two genes involved in regulation of toxins A and B, tcdC and tcdR 17 . So far the most detailed study has included ten strains from 6 ribotypes (027, 078 and four local designations) and four toxinotypes (III, IV, V, IX) 18 . They could differentiate the CdtLoc into three groups which largely overlap with ribotypes and toxinotypes.…”

Section: Cdtloc: Binary Toxin Encoding Locusmentioning

confidence: 99%

Clostridium difficilebinary toxin CDT

et al. 2013

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Binary toxin (CDT) is frequently observed in Clostridium difficile strains associated with increased severity of C. difficile infection (CDI). CDT belongs to the family of binary ADP-ribosylating toxins consisting of two separate toxin components: CDTa, the enzymatic ADP-ribosyltransferase which modifies actin, and CDTb which binds to host cells and translocates CDTa into the cytosol. CDTb is activated by serine proteases and binds to lipolysis stimulated lipoprotein receptor. ADP-ribosylation induces depolymerization of the actin cytoskeleton. Toxin-induced actin depolymerization also produces microtubule-based membrane protrusions which form a network on epithelial cells and increase bacterial adherence. Multiple clinical studies indicate an association between binary toxin genes in C. difficile and increased 30-d CDI mortality independent of PCR ribotype. Further studies including measures of binary toxin in stool, analyses of CDI mortality caused by CDT-producing strains, and examination of the relationship of CDT expression to TcdA and TcdB toxin variants and PCR ribotypes are needed.

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Binary toxin locus analysis in Clostridium difficile

Cited by 19 publications

References 27 publications

Clostridium difficile infection

Clostridium difficile infection

Pore-forming activity of clostridial binary toxins

Clostridium difficilebinary toxin CDT

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