{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:20:59Z","timestamp":1760242859824,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2016,12,22]],"date-time":"2016-12-22T00:00:00Z","timestamp":1482364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Volkswagen Stiftung","award":["VWZN3215"],"award-info":[{"award-number":["VWZN3215"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Lethal Toxin from Clostridium sordellii (TcsL), which is casually involved in the toxic shock syndrome and in gas gangrene, enters its target cells by receptor-mediated endocytosis. Inside the cell, TcsL mono-O-glucosylates and thereby inactivates Rac\/Cdc42 and Ras subtype GTPases, resulting in actin reorganization and an activation of p38 MAP kinase. While a role of p38 MAP kinase in TcsL-induced cell death is well established, data on a role of p38 MAP kinase in TcsL-induced actin reorganization are not available. In this study, TcsL-induced Rac\/Cdc42 glucosylation and actin reorganization are differentially analyzed in p38alpha\u2212\/\u2212 MSCV empty vector MEFs and the corresponding cell line with reconstituted p38alpha expression (p38alpha\u2212\/\u2212 MSCV p38alpha MEFs). Genetic deletion of p38alpha results in reduced susceptibility of cells to TcsL-induced Rac\/Cdc42 glucosylation and actin reorganization. Furthermore, SB203580, a pyridinyl imidazole inhibitor of p38alpha\/beta MAP kinase, also protects cells from TcsL-induced effects in both p38\u2212\/\u2212 MSCV empty vector MEFs and in p38alpha\u2212\/\u2212 MSCV p38alpha MEFs, suggesting that inhibition of p38beta contributes to the protective effect of SB203580. In contrast, the effects of the related C. difficile Toxin B are responsive neither to SB203580 treatment nor to p38alpha deletion. In conclusion, the protective effects of SB203580 and of p38alpha deletion are likely not based on inhibition of the toxins\u2019 glucosyltransferase activity rather than on inhibited endocytic uptake of specifically TcsL into target cells.<\/jats:p>","DOI":"10.3390\/toxins9010002","type":"journal-article","created":{"date-parts":[[2016,12,22]],"date-time":"2016-12-22T09:48:53Z","timestamp":1482400133000},"page":"2","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Role of p38alpha\/beta MAP Kinase in Cell Susceptibility to Clostridium sordellii Lethal Toxin and Clostridium difficile Toxin B"],"prefix":"10.3390","volume":"9","author":[{"given":"Ilona","family":"Schelle","sequence":"first","affiliation":[{"name":"Institute for Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janina","family":"Bruening","sequence":"additional","affiliation":[{"name":"Institute for Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mareike","family":"Buetepage","sequence":"additional","affiliation":[{"name":"Institute for Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Genth","sequence":"additional","affiliation":[{"name":"Institute for Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1097\/MOG.0b013e32835b422c","article-title":"Bacterial infections of the small intestine","volume":"29","author":"Hodges","year":"2013","journal-title":"Curr. 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