Comparative study of immunological properties and cytotoxic effects of Clostridium difficile toxin B and Clostridium sordellii toxin L

Baldacini, Olivier; Girardot, Raymonde; Green, Gaynor A.; Rihn, Bertrand; Monteil, H.

doi:10.1016/0041-0101(92)90466-i

Cited by 16 publications

(9 citation statements)

References 32 publications

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“…Lethal toxin, a glucosyltransferase causally associated with severe edemas, was found to be a potent disruptive agent in human endothelial monolayers. Overnight treatment with 400 ϫ 10 Ϫ12 M toxin resulted in extensive cell rounding and detachment, similar to the previously described effect of the toxin on different cell types (1,3,15). Interestingly, 10-to 100-fold-lower doses of lethal toxin induced cell elongation with noticeable increases in stress fiber formation rather than a decrease in actin microfilaments, which has been previously documented.…”

Section: Discussionsupporting

confidence: 86%

Effects of Cytotoxic Necrotizing Factor 1 and Lethal Toxin on Actin Cytoskeleton and VE-Cadherin Localization in Human Endothelial Cell Monolayers

Vouret‐Craviari¹,

Grall²,

Flatau

et al. 1999

Infect Immun

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Integrity of the vascular endothelium is largely dependent on endothelial cell shape and establishment of intercellular junctions. Certain pathogenic bacterial toxins alter the cytoskeletal architecture of intoxicated cells by modulating the GTPase activity of p21 Rho family proteins. In the present study we have analyzed the effect of Rho-directed toxins on the actin cytoskeleton and monolayer integrity of endothelial cells. We report here that Escherichia colicytotoxic necrotizing factor 1 (CNF1) activates Rho in human umbilical vein endothelial cells (HUVEC). In confluent monolayers, CNF1 treatment induces prominent stress fiber formation without significantly modifying peripheral localization of VE-cadherin, a specific marker of vascular endothelial cell adherens junctions. Further, Rho activation with CNF1 blocks thrombin-induced redistribution of VE-cadherin staining and gap formation in HUVEC monolayers. Inhibition of Rho by prolonged treatment of cells with C3 exoenzyme (Clostridium botulinum) eliminates actin stress fibers without disrupting the continuity of VE-cadherin staining, indicating that Rho-dependent stress fibers are not required for maintaining this adhesion receptor at sites of intercellular contact. Lethal toxin (Clostridium sordellii), an inhibitor of Rac as well as Ras and Rap, potently disrupts the actin microfilament system and monolayer integrity in HUVEC cultures.

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Section: Discussionsupporting

confidence: 86%

Effects of Cytotoxic Necrotizing Factor 1 and Lethal Toxin on Actin Cytoskeleton and VE-Cadherin Localization in Human Endothelial Cell Monolayers

Vouret‐Craviari¹,

Grall²,

Flatau

et al. 1999

Infect Immun

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“…Clostridium dif¼cile toxin A (TxA) is a large, multidomain carbohydrate-binding protein, which is an enterotoxin with 2710 aminoacids (asparagine, glicine and glutamine being the most abundant) and 308 kDa molecular weight (Banno et al, 1984;Baldacini et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Role of phospholipase A₂ and tyrosine kinase in Clostridium difficile toxin A‐induced disruption of epithelial integrity, histologic inflammatory damage and intestinal secretion

Lima

Nascimento

Fang

et al. 2008

J of Applied Toxicology

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Clostridium difficile-associated disease causes diarrhea to fulminant colitis and death. We investigated the role of phospholipase A2 (PLA2) inhibitors, aristolochic acid (AA), bromophenacyl bromide (BPB) and quinacrine (QUIN) on the C. difficile toxin A-induced disruption of epithelial integrity, histologic inflammatory damage and intestinal secretion. Toxin A caused severe hemorrhagic and inflammatory fluid secretion at 6-8 h in rabbit ileal segments, an effect that was significantly inhibited by QUIN (71%, P < 0.01), AA (87%, P < 0.000l) or by BPB (51%, P < 0.01). The secretory effect of toxin A was also inhibited in segments adjacent to those with AA (89%, P < 0.01). Furthermore, QUIN or AA substantially reduced the histologic damage seen after 6-8 h in rabbit ileal segments. The cyclooxygenase inhibitor, indomethacin, also significantly inhibited (96%; n = 6) the secretory effects of toxin A in ligated rabbit intestinal segments. The destruction by toxin A of F-actin at the tight junctions of T-84 cell monolayers was not inhibited by AA or BPB. AA or QUIN had no effect on the T-84 cell tissue resistance reduction over 8-24 h after toxin A exposure. All the inhibitors were shown to be effective in the doses administered direct in ileal loops to inhibit PLA2 activity. The data suggest that PLA2 is involved in the major pathway of toxin A-induced histologic inflammatory damage and hemorrhagic fluid secretion.

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“…The cytotoxic effects of C. sordellii LT differ from those of C. difficile ToxB (2,7,19,22). For example, ToxB induces massive retraction and arborization of CHO cells whereas LT causes rounding up without major retraction and arborization (22).…”

Section: Discussionmentioning

confidence: 99%

“…The LT from Clostridium sordellii is another member of the family of large clostridial cytotoxins (2,4,8). This toxin, with a molecular mass of ϳ270 kDa, is involved in gas gangrene in humans and diarrhea and enterotoxemia in domestic animals (9,20).…”

mentioning

confidence: 99%

Chimeric Clostridial Cytotoxins: Identification of the N-Terminal Region Involved in Protein Substrate Recognition

1998

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Clostridium sordellii lethal toxin is a member of the family of large clostridial cytotoxins that glucosylate small GTPases. In contrast to Clostridium difficile toxins A and B, which exclusively modify Rho subfamily proteins, C. sordelliilethal toxin also glucosylates Ras subfamily proteins. By deletion analysis and construction of chimeric fusion proteins of C. sordellii lethal toxin and C. difficile toxin B, we localized the enzyme activity of the lethal toxin to the N terminus of the holotoxin and identified the region involved in protein substrate specificity. The toxin fragment of the N-terminal 546 amino acid residues of C. sordellii lethal toxin glucosylated Rho and Ras subfamily proteins, as the holotoxin did. Deletion of a further 30 amino acid residues from the C terminus of this active fragment drastically reduced glucotransferase activity and blocked glucohydrolase activity. Exchange of amino acid residues 364 through 516 of lethal toxin for those in the active toxin B fragment (1 to 546) allowed glucosylation of Ras subfamily proteins. In contrast, the chimera with amino acids 1 to 364 from toxin B, 365 to 468 from lethal toxin, and 469 to 546 from toxin B exhibited markedly reduced modification of Ras subfamily proteins, whereas modification of Rac and Cdc42 was hardly changed. The data indicate that the region of amino acid residues 364 through 516 primarily defines the substrate specificity of C. sordellii lethal toxin.

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Comparative study of immunological properties and cytotoxic effects of Clostridium difficile toxin B and Clostridium sordellii toxin L

Cited by 16 publications

References 32 publications

Effects of Cytotoxic Necrotizing Factor 1 and Lethal Toxin on Actin Cytoskeleton and VE-Cadherin Localization in Human Endothelial Cell Monolayers

Effects of Cytotoxic Necrotizing Factor 1 and Lethal Toxin on Actin Cytoskeleton and VE-Cadherin Localization in Human Endothelial Cell Monolayers

Role of phospholipase A₂ and tyrosine kinase in Clostridium difficile toxin A‐induced disruption of epithelial integrity, histologic inflammatory damage and intestinal secretion

Chimeric Clostridial Cytotoxins: Identification of the N-Terminal Region Involved in Protein Substrate Recognition

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Comparative study of immunological properties and cytotoxic effects of Clostridium difficile toxin B and Clostridium sordellii toxin L

Cited by 16 publications

References 32 publications

Effects of Cytotoxic Necrotizing Factor 1 and Lethal Toxin on Actin Cytoskeleton and VE-Cadherin Localization in Human Endothelial Cell Monolayers

Effects of Cytotoxic Necrotizing Factor 1 and Lethal Toxin on Actin Cytoskeleton and VE-Cadherin Localization in Human Endothelial Cell Monolayers

Role of phospholipase A2 and tyrosine kinase in Clostridium difficile toxin A‐induced disruption of epithelial integrity, histologic inflammatory damage and intestinal secretion

Chimeric Clostridial Cytotoxins: Identification of the N-Terminal Region Involved in Protein Substrate Recognition

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Role of phospholipase A₂ and tyrosine kinase in Clostridium difficile toxin A‐induced disruption of epithelial integrity, histologic inflammatory damage and intestinal secretion