{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T20:39:00Z","timestamp":1776285540538,"version":"3.50.1"},"reference-count":183,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Clostridioides difficile (C. difficile), responsible for 15\u201325% of gastrointestinal infections, causes health problems mainly due to the toxic activity of toxins A and B (Tcds). These are responsible for its clinical manifestations, including diarrhea, pseudomembranous colitis, toxic megacolon and death, with a mortality of 5\u201330% in primary infection, that increase following relapses. Studies on Tcd-induced cell death have highlighted a key role of caspases, calpains, and cathepsins, with involvement of mitochondria and reactive oxygen species (ROS) in a complex signaling pathway network. The complex response in the execution of various types of cell death (apoptosis, necrosis, pyroptosis and pyknosis) depends on the amount of Tcd, cell types, and Tcd receptors involved, and could have as initial\/precocious event the alterations in calcium homeostasis. The entities, peculiarities and cell types involved in these alterations will decide the signaling pathways activated and cell death type. Calcium homeostasis alterations can be caused by calcium influx through calcium channel activation, transient intracellular calcium oscillations, and leakage of calcium from intracellular stores. These increases in cytoplasmic calcium have important effects on all calcium-regulated molecules, which may play a direct role in several cell death types and\/or activate other cell death effectors, such as caspases, calpains, ROS and proapoptotic Bcl-2 family members. Furthermore, some support for the possible role of the calcium homeostasis alteration in Tcd-induced cell death originates from the similarity with cytotoxic effects that cause pore-forming toxins, based mainly on calcium influx through plasma membrane pores.<\/jats:p>","DOI":"10.3390\/biology12081117","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T10:11:22Z","timestamp":1691662282000},"page":"1117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Role of the Alteration in Calcium Homeostasis in Cell Death Induced by Clostridioides difficile Toxin A and Toxin B"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8074-8243","authenticated-orcid":false,"given":"Katia","family":"Fettucciari","sequence":"first","affiliation":[{"name":"Biosciences & Medical Embryology Section, Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Dini","sequence":"additional","affiliation":[{"name":"School of Biosciences and Veterinary Medicine, University of Camerino, 62024 Matelica, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierfrancesco","family":"Marconi","sequence":"additional","affiliation":[{"name":"Biosciences & Medical Embryology Section, Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0237-1812","authenticated-orcid":false,"given":"Gabrio","family":"Bassotti","sequence":"additional","affiliation":[{"name":"Gastroenterology, Hepatology & Digestive Endoscopy Section, Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy"},{"name":"Gastroenterology & Hepatology Unit, Santa Maria Della Misericordia Hospital, 06129 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.anaerobe.2018.07.005","article-title":"Clostridium difficile and Clostridioides difficile: Two validly published and correct names","volume":"52","author":"Oren","year":"2018","journal-title":"Anaerobe"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.anaerobe.2016.06.008","article-title":"Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O\u2019Toole 1935) Pr\u00e9vot 1938","volume":"40","author":"Lawson","year":"2016","journal-title":"Anaerobe"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"010407","DOI":"10.7189\/jogh.09.010407","article-title":"Global burden of Clostridium difficile infections: A systematic review and meta-analysis","volume":"9","author":"Balsells","year":"2019","journal-title":"J. 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