Clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis.

Clostridium difficile toxin A (TcdA) and toxin B (TcdB), C. sordellii lethal toxin (TcsL) and C. novyi alpha-toxin (TcnA) are important pathogenicity factors, which represent the family of the clostridial glucosylating toxins (CGTs). Toxin A and B are associated with antibiotic-associated diarrhea a...

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Autores principales:	Panagiotis Papatheodorou, Constantinos Zamboglou, Selda Genisyuerek, Gregor Guttenberg, Klaus Aktories
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6d55c26786ba4fe9ae94fe055c128f32
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spelling	oai:doaj.org-article:6d55c26786ba4fe9ae94fe055c128f322021-12-02T20:21:37ZClostridial glucosylating toxins enter cells via clathrin-mediated endocytosis.1932-620310.1371/journal.pone.0010673https://doaj.org/article/6d55c26786ba4fe9ae94fe055c128f322010-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20498856/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Clostridium difficile toxin A (TcdA) and toxin B (TcdB), C. sordellii lethal toxin (TcsL) and C. novyi alpha-toxin (TcnA) are important pathogenicity factors, which represent the family of the clostridial glucosylating toxins (CGTs). Toxin A and B are associated with antibiotic-associated diarrhea and pseudomembraneous colitis. Lethal toxin is involved in toxic shock syndrome after abortion and alpha-toxin in gas gangrene development. CGTs enter cells via receptor-mediated endocytosis and require an acidified endosome for translocation of the catalytic domain into the cytosol. Here we studied the endocytic processes that mediate cell internalization of the CGTs. Intoxication of cells was monitored by analyzing cell morphology, status of Rac glucosylation in cell lysates and transepithelial resistance of cell monolayers. We found that the intoxication of cultured cells by CGTs was strongly delayed when cells were preincubated with dynasore, a cell-permeable inhibitor of dynamin, or chlorpromazine, an inhibitor of the clathrin-dependent endocytic pathway. Additional evidence about the role of clathrin in the uptake of the prototypical CGT family member toxin B was achieved by expression of a dominant-negative inhibitor of the clathrin-mediated endocytosis (Eps15 DN) or by siRNA against the clathrin heavy chain. Accordingly, cells that expressed dominant-negative caveolin-1 were not protected from toxin B-induced cell rounding. In addition, lipid rafts impairment by exogenous depletion of sphingomyelin did not decelerate intoxication of HeLa cells by CGTs. Taken together, our data indicate that the endocytic uptake of the CGTs involves a dynamin-dependent process that is mainly governed by clathrin.Panagiotis PapatheodorouConstantinos ZamboglouSelda GenisyuerekGregor GuttenbergKlaus AktoriesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 5, p e10673 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Panagiotis Papatheodorou Constantinos Zamboglou Selda Genisyuerek Gregor Guttenberg Klaus Aktories Clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis.
description	Clostridium difficile toxin A (TcdA) and toxin B (TcdB), C. sordellii lethal toxin (TcsL) and C. novyi alpha-toxin (TcnA) are important pathogenicity factors, which represent the family of the clostridial glucosylating toxins (CGTs). Toxin A and B are associated with antibiotic-associated diarrhea and pseudomembraneous colitis. Lethal toxin is involved in toxic shock syndrome after abortion and alpha-toxin in gas gangrene development. CGTs enter cells via receptor-mediated endocytosis and require an acidified endosome for translocation of the catalytic domain into the cytosol. Here we studied the endocytic processes that mediate cell internalization of the CGTs. Intoxication of cells was monitored by analyzing cell morphology, status of Rac glucosylation in cell lysates and transepithelial resistance of cell monolayers. We found that the intoxication of cultured cells by CGTs was strongly delayed when cells were preincubated with dynasore, a cell-permeable inhibitor of dynamin, or chlorpromazine, an inhibitor of the clathrin-dependent endocytic pathway. Additional evidence about the role of clathrin in the uptake of the prototypical CGT family member toxin B was achieved by expression of a dominant-negative inhibitor of the clathrin-mediated endocytosis (Eps15 DN) or by siRNA against the clathrin heavy chain. Accordingly, cells that expressed dominant-negative caveolin-1 were not protected from toxin B-induced cell rounding. In addition, lipid rafts impairment by exogenous depletion of sphingomyelin did not decelerate intoxication of HeLa cells by CGTs. Taken together, our data indicate that the endocytic uptake of the CGTs involves a dynamin-dependent process that is mainly governed by clathrin.
format	article
author	Panagiotis Papatheodorou Constantinos Zamboglou Selda Genisyuerek Gregor Guttenberg Klaus Aktories
author_facet	Panagiotis Papatheodorou Constantinos Zamboglou Selda Genisyuerek Gregor Guttenberg Klaus Aktories
author_sort	Panagiotis Papatheodorou
title	Clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis.
title_short	Clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis.
title_full	Clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis.
title_fullStr	Clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis.
title_full_unstemmed	Clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis.
title_sort	clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/6d55c26786ba4fe9ae94fe055c128f32
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Clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis.

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