Clostridium perfringens ε-Toxin Forms a Heptameric Pore within the Detergent-insoluble Microdomains of Madin-Darby Canine Kidney Cells and Rat Synaptosomes

Miyata, Seiko; Minami, Junzaburo; Tamai, Eiji; Matsushita, Osamu; Shimamoto, Seiko; Okabe, Akinobu

doi:10.1074/jbc.m206731200

Cited by 130 publications

(146 citation statements)

References 38 publications

(50 reference statements)

Supporting

Mentioning

138

Contrasting

Unclassified

Order By: Relevance

“…Epsilon toxin binds to a specific receptor on a restricted number of cell lines, which is distinct from GPI-anchored proteins recognized by aerolysin. However, epsilon toxin heptamerizes and induces pore formation in target cells, leading to a rapid change in cell membrane permeability and cell death (Petit et al, 1997(Petit et al, , 2003Miyata et al, 2002).…”

Section: Heptameric β-Pfts Forming Small Pores Aerolysin and Related mentioning

confidence: 99%

Bacterial protein toxins and lipids: pore formation or toxin entry into cells

Geny

Popoff

2006

Biology of the Cell

118

104

View full text Add to dashboard Cite

Lipids are hydrophobic molecules which play critical functions in cells, in particular, they are essential constituents of membranes, whereas bacterial toxins are mainly hydrophilic proteins. All bacterial toxins interact first with their target cells by recognizing a surface receptor, which is either a lipid or a lipid derivative, or another compound but in a lipid environment. Most bacterial toxins are PFTs (pore‐forming toxins) which oligomerize and insert into the lipid bilayer. A common mechanism of action involves the formation of a β‐barrel structure, resulting from the assembly of individual β‐hairpin(s) from individual monomers. An essential step for intracellular active toxins is to translocate their enzymatic part into the cytosol. Some toxins use a translocation mechanism based on pore formation similar to that of PFTs, others undergo a yet unclear ‘chaperone’ process.

show abstract

Section: Heptameric β-Pfts Forming Small Pores Aerolysin and Related mentioning

confidence: 99%

Bacterial protein toxins and lipids: pore formation or toxin entry into cells

Geny

Popoff

2006

Biology of the Cell

118

104

View full text Add to dashboard Cite

show abstract

“…To overcome these problems it is necessary not only to standardize the ET assay system but also to examine the molecular mechanism of ET cytotoxicity. Considering that ET preferentially binds to and forms a heptamer within the DRMs of MDCK cells (12), it can be assumed that changes in the components of DRMs may be associated with the variation in the ET susceptibility of MDCK cells, although the distribution and/or amounts of a putative ET receptor may also be associated with it. The effects of cholesterol depletion by a cholesterol synthesis inhibitor and methyl-β-cyclodextrin treatment on ET binding and heptamerization has been examined (12).…”

mentioning

confidence: 99%

“…Considering that ET preferentially binds to and forms a heptamer within the DRMs of MDCK cells (12), it can be assumed that changes in the components of DRMs may be associated with the variation in the ET susceptibility of MDCK cells, although the distribution and/or amounts of a putative ET receptor may also be associated with it. The effects of cholesterol depletion by a cholesterol synthesis inhibitor and methyl-β-cyclodextrin treatment on ET binding and heptamerization has been examined (12). However, possible effects of changes in other lipid constituents of DRMs, such as sphingomyelin and glycosphingolipids, on the ET binding and heptamerization have not yet been examined.…”

mentioning

confidence: 99%

Changes in Ganglioside Content Affect the Binding of Clostridium perfringens Epsilon‐Toxin to Detergent‐Resistant Membranes of Madin‐Darby Canine Kidney Cells

Shimamoto

Tamai

Matsushita

et al. 2005

Microbiology and Immunology

Self Cite

View full text Add to dashboard Cite

Epsilon‐toxin (ET) of Clostridium perfringens, which causes fatal enterotoxemia in ungulates, was previously shown to bind to and form a heptameric pore within the detergent‐resistant membranes (DRMs) of MDCK cells. Depletion of cholesterol has also been shown to decrease the cytotoxicity of ET and its heptamerization. In this study, we investigated the effects of changes in sphingolipids, other DRM components of MDCK cells, on the cells' susceptibility to ET. Treatment with fumonisin B1 and PDMP, inhibitors of sphingolipid and glycosphingolipid syntheses, respectively, increased the susceptibility, while D609, a sphingomyelin synthesis inhibitor, had the opposite effect. The exogenous addition of ganglioside GM1 dramatically decreased the ET binding, heptamerization and cytotoxicity. These effects were shown not to be due to ET binding to GM1 or to denaturation of ET. We also found that the ET cytotoxicity towards MDCK cells decreased with an increase in culture time. In accordance with the resistance observed for prolonged cultured cells, GM3, a major ganglioside component, increased and sialidase treatment increased their susceptibility. These results suggest that membrane‐anchored sialic acid of GM3 within DRMs inhibits ET binding, leading to prevention of the heptamerization of ET and cell death. It is also suggested that sialidase produced by this organism aids the targeting of ET to MDCK cells.

show abstract

“…(Miyata et al 2002). Προκαλεί αύξηση της αρτηριακής πίεσης και της αρτηριακής διαπερατότητας, με αποτέλεσμα να διευκολύνεται η διέλευση της από το γαστρεντερικό βλεννογόνο, να εισέρχεται στην κυκλοφορία του αίμα τος και να μεταφέρεται σε διάφορα όργανα του σώμα τος, όπως στον εγκέφαλο, την καρδιά, τους πνεύμονες και τους νεφρούς, προκαλώντας βλάβες στο ενδοθήλιο των αγγείων, απώλεια υγρών, οίδημα και αιμορραγίες (Tamai et al 2003).…”

Section: τοξίνη -εunclassified

“…Μετά τη σύνδεση της με τους κυτταρικούς υποδοχείς, προκαλεί μη επιλεκτικά πόρους με ολι-γομερισμότης κυτταρικής μεμβράνης, με αποτέλεσμα την απώλεια της επιθηλιακής ανθεκτικότητας. Αυτό έχει ως αποτέλεσμα τη συγκέντρωση υγρού και την πρόκληση οιδήματος στον προσβεβλημένο ιστό (Petit et al 2001, Miyata et al 2002.…”

Section: τοξίνη -εunclassified

Update on the toxins of Clostridium perfringens and their actions

Tsiouris

Georgopoulou

Petridou

2017

J Hellenic Vet Med Soc

View full text Add to dashboard Cite

Clostridia appeared as a distinct class, approximately 2.7 billion years ago, before the initial formation of oxygen. Clostridium perfringens is widely distributed throughout the environment due to its ability to form spores. Furthermore, it is a member of intestinal microbiota in animals and human. In 2002, the complete genome of C perfringens strain 13 was published. Genomic analysis has revealed that C. perfringens lacks the genetic machinery to produce 13 essential amino acids and it obtains these in vivo via the action of its toxins. Toxins of C perfringens can be divided into major, minor and enterotoxin. C perfringens strains are classified into five toxinotypes (A, B, C, D and E), based on the production of four major toxins. Alpha toxin is the best and most studied major toxin of C perfringens and it was the first bacterial toxin established to possess enzymatic activity. It has haemolytic, necrotic and cytolytic activity, it can lyse platelets and leukocytes and it can damage fibroblasts and muscle cell membranes. Expression of epa gene, which is responsible for the production of alpha toxin by C perfringens, is down-regulated in the normal healthy gut, but it is upregulated to initiate enteric disease in response to an environmental signal. C perfringens appears to be regulated in a quorum sensing manner, using oligopeptides, AI-2 or both, to regulate expression of the epa gene, and thus the synthesis of alpha toxin. Beta toxin is recognized as an important agent in necrotic enteritis of humans and it is the second most lethal C. perfringens toxin following epsilon toxin. Beta toxin is a membrane spanning protein that oligomerizes to form channels in susceptible cells or it primarily acts as a neurotoxin. Epsilon toxin is the most potent of the C. perfringens toxins and the third most potent neurotoxin from the Clostridium spp., following botulinum and tetanus toxins. Epsilon toxin of C perfringens type D causes enterotoxaemia and pulpy kidneys disease of lambs. Iota toxin causes disruption of the actin cytoskeleton and cell barrier integrity and it is the less toxic of the major toxins of C perfringens. Although C perfringens enterotoxin is not classified as one of the major toxins of C perfringens, it is the third most common cause of food poisoning in industrialized nations. It is not secreted by the cells of growing bacteria, but it is released only with the sporulation of C perfringens. Not all strains of C perfringens carry the epe gene, which is responsible for the production of enterotoxin. Theta toxin is a pore-forming cytolysin that can lyse red blood cells. It is produced by all types of C perfringens. Together with alpha-toxin, theta-toxin modulates the host inflammatory response. ß2 toxin is a pore forming toxin which is involved in necrotic enteritis of swine and horse, in haemorragic enteritis of bovine in diarrhea cases of dogs and along with enterotoxin in diarrhea cases of humans. Recently, -NetB, a novel toxin that is associated with broiler necrotic enteritis, has been described. The mechanism of its action seems to involve the formation of small hydrophilic pores. Other toxins of C. perfringens include λ-toxin, ô-toxin, μ-toxin, v-toxin, κ-toxin, a-clostripain like protease and neuraminidase/sialidase. These toxins can act as enzymes, while many of them can act synergically or supplementally with major pore forming toxins. Potentially, C. perfringens might produce more toxins, which have not been identified. Finally, the actions of C. perfringens toxins, major or minor, in some diseases have not been figured out.

show abstract

Clostridium perfringens ε-Toxin Forms a Heptameric Pore within the Detergent-insoluble Microdomains of Madin-Darby Canine Kidney Cells and Rat Synaptosomes

Cited by 130 publications

References 38 publications

Bacterial protein toxins and lipids: pore formation or toxin entry into cells

Bacterial protein toxins and lipids: pore formation or toxin entry into cells

Changes in Ganglioside Content Affect the Binding of Clostridium perfringens Epsilon‐Toxin to Detergent‐Resistant Membranes of Madin‐Darby Canine Kidney Cells

Update on the toxins of Clostridium perfringens and their actions

Contact Info

Product

Resources

About