{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:13:07Z","timestamp":1790817187088,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The alarming symptoms attributed to several potent clostridial toxins enabled the early identification of the causative agent of tetanus, botulism, and gas gangrene diseases, which belongs to the most famous species of pathogenic clostridia. Although Clostridioides difficile was identified early in the 20th century as producing important toxins, it was identified only 40 years later as the causative agent of important nosocomial diseases upon the advent of antibiotic therapies in hospital settings. Today, C. difficile is a leading public health issue, as it is the major cause of antibiotic-associated diarrhea in adults. In particular, severe symptoms within the spectrum of C. difficile infections are directly related to the levels of toxins produced in the host. This highlights the importance of understanding the regulation of toxin synthesis in the pathogenicity process of C. difficile, whose regulatory factors in response to the gut environment were first identified at the Institut Pasteur. Subsequently, the work of other groups in the field contributed to further deciphering the complex mechanisms controlling toxin production triggered by the intestinal dysbiosis states during infection. This review summarizes the Pasteurian contribution to clostridial toxin regulation studies.<\/jats:p>","DOI":"10.3390\/toxins15070413","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T03:14:56Z","timestamp":1687749296000},"page":"413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Regulation of Clostridial Toxin Gene Expression: A Pasteurian Tradition"],"prefix":"10.3390","volume":"15","author":[{"given":"Bruno","family":"Dupuy","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris-Cit\u00e9, UMR-CNRS 6047, Laboratoire Pathogen\u00e8se des Bact\u00e9ries Ana\u00e9robies, F-75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1038\/nrmicro2164","article-title":"Clostridium difficile infection: New developments in epidemiology and pathogenesis","volume":"7","author":"Rupnik","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/375500a0","article-title":"Glucosylation of Rho proteins by Clostridium difficile toxin B","volume":"375","author":"Just","year":"1995","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Di Bella, S., Ascenzi, P., Siarakas, S., Petrosillo, N., and di Masi, A. (2016). Clostridium difficile Toxins A and B: Insights into Pathogenic Properties and Extraintestinal Effects. Toxins, 8.","DOI":"10.3390\/toxins8050134"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1111\/cmi.12533","article-title":"Bacterial glycosyltransferase toxins","volume":"17","author":"Jank","year":"2015","journal-title":"Cell. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1136\/jcp.40.12.1397","article-title":"Association between production of toxins A and B and types of Clostridium difficile","volume":"40","author":"Wren","year":"1987","journal-title":"J. Clin. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1128\/JCM.44.2.353-358.2006","article-title":"Correlation of disease severity with fecal toxin levels in patients with Clostridium difficile-associated diarrhea and distribution of PCR ribotypes and toxin yields in vitro of corresponding isolates","volume":"44","author":"Akerlund","year":"2006","journal-title":"J. Clin. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/S0140-6736(05)67420-X","article-title":"Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe","volume":"366","author":"Warny","year":"2005","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4904","DOI":"10.1128\/JB.00445-10","article-title":"Human hypervirulent Clostridium difficile strains exhibit increased sporulation as well as robust toxin production","volume":"192","author":"Merrigan","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1046\/j.1365-2958.1998.00663.x","article-title":"Regulated transcription of Clostridium difficile toxin genes","volume":"27","author":"Dupuy","year":"1998","journal-title":"Mol. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1111\/j.1432-1033.1997.t01-1-00735.x","article-title":"Transcription analysis of the genes tcdA-E of the pathogenicity locus of Clostridium difficile","volume":"244","author":"Hundsberger","year":"1997","journal-title":"Eur. J. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1099\/00222615-44-2-111","article-title":"Enhancement of Clostridium difficile toxin production in biotin-limited conditions","volume":"44","author":"Yamakawa","year":"1996","journal-title":"J. Med. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5881","DOI":"10.1128\/IAI.68.10.5881-5888.2000","article-title":"JToxins, butyric acid and other short-chain fatty acids are coordinately expressed and down regulated by cysteine in Clostridium difficile","volume":"68","author":"Karlsson","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1099\/13500872-145-7-1683","article-title":"Suppression of toxin production in Clostridium difficile VPI 10463 by amino acids","volume":"145","author":"Karlsson","year":"1999","journal-title":"Microbiology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3430","DOI":"10.1099\/mic.0.2008\/019778-0","article-title":"Induction of toxins in Clostridium difficile is associated with dramatic changes of its metabolism","volume":"154","author":"Karlsson","year":"2008","journal-title":"Microbiology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1111\/j.1365-2958.2010.07495.x","article-title":"CcpA-mediated repression of Clostridium difficile toxin gene expression","volume":"79","author":"Antunes","year":"2011","journal-title":"Mol. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1128\/JB.01492-12","article-title":"Proline-dependent regulation of Clostridium difficile Stickland metabolism","volume":"195","author":"Bouillaut","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1128\/IAI.00121-16","article-title":"Control of Clostridium difficile physiopathology in response to cysteine availability","volume":"84","author":"Dubois","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_18","first-page":"375","article-title":"Integration of metabolism and virulence in Clostridium difficile","volume":"164","author":"Bouillaut","year":"2014","journal-title":"Res. Microbiol. Rev"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0378-1119(96)00398-8","article-title":"Definition of the single integration site of the pathogenicity locus in Clostridium difficile","volume":"181","author":"Braun","year":"1996","journal-title":"Gene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1093\/gbe\/evt204","article-title":"Evolutionary history of the Clostridium difficile pathogenicity locus","volume":"6","author":"Dingle","year":"2014","journal-title":"Genome Biol. Evol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15023","DOI":"10.1038\/srep15023","article-title":"Clostridium difficile: New Insights into the Evolution of the Pathogenicity Locus","volume":"5","author":"Monot","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1128\/JCM.02211-14","article-title":"A new type of toxin A-negative, toxin B-positive Clostridium difficile strain lacking a complete tcdA gene","volume":"53","author":"Janezic","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0882-4010(87)90073-8","article-title":"Purification of two high molecular weight toxins of Clostridium difficile which are antigenically related","volume":"2","author":"Harperath","year":"1987","journal-title":"Microb. Pathog."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.1128\/JB.00711-13","article-title":"Identification and characterization of Clostridium sordellii toxin gene regulator","volume":"195","author":"Girinathan","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1111\/j.1365-2958.2004.04456.x","article-title":"Transcription activation of a UV-inducible Clostridium perfringens bacteriocin gene by a novel sigma factor","volume":"55","author":"Dupuy","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/j.1365-2958.2004.04377.x","article-title":"BotR\/A and TetR are alternative RNA polymerase sigma factors controlling the expression of the neurotoxin and associated protein genes in Clostridium botulinum type A and Clostridium tetani","volume":"55","author":"Raffestin","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.ijmm.2014.08.008","article-title":"Expression of the large clostridial toxins is controlled by conserved regulatory mechanisms","volume":"304","author":"Carter","year":"2014","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00580-20","DOI":"10.1128\/JB.00580-20","article-title":"Holin-Dependent Secretion of the Large Clostridial Toxin TpeL by Clostridium perfringens","volume":"203","author":"Saadat","year":"2021","journal-title":"J. Bacteriol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1128\/iai.65.3.1105-1108.1997","article-title":"Positive regulation of Clostridium difficile toxins","volume":"65","author":"Moncrief","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5844","DOI":"10.1073\/pnas.101126598","article-title":"Regulation of toxin synthesis in Clostridium difficile by an alternative RNA polymerase sigma factor","volume":"98","author":"Mani","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/mmi.14107","article-title":"Multiple factors contribute to bimodal toxin gene expression in Clostridioides (Clostridium) difficile","volume":"110","author":"Ransom","year":"2018","journal-title":"Mol. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5971","DOI":"10.1128\/JB.184.21.5971-5978.2002","article-title":"Environmental response and autoregulation of Clostridium difficile TxeR, a sigma factor for toxin gene expression","volume":"184","author":"Mani","year":"2002","journal-title":"J. Bacteriol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1111\/j.1365-2958.2007.05739.x","article-title":"Clostridium difficile toxin expression is inhibited by the novel regulator TcdC","volume":"64","author":"Matamouros","year":"2007","journal-title":"Mol. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"El Meouche, I., Peltier, J., Monot, M., Soutourina, O., Pestel-Caron, M., Dupuy, B., and Pons, J.L. (2013). Characterization of the SigD regulon of Clostridium difficile and its positive control of toxin production through the regulation of tcdR. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083748"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10701","DOI":"10.1093\/nar\/gks864","article-title":"Global transcriptional control by glucose and carbon regulator CcpA in Clostridium difficile","volume":"40","author":"Antunes","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1365-2958.2007.05906.x","article-title":"Repression of Clostridium difficile toxin gene expression by CodY","volume":"66","author":"Dineen","year":"2007","journal-title":"Mol. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1111\/j.1365-2958.2006.05159.x","article-title":"Regulation of toxin and bacteriocin gene expression in Clostridium by interchangeable RNA polymerase sigma factors","volume":"60","author":"Dupuy","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.1128\/JB.188.10.3716-3720.2006","article-title":"Evidence that Clostridium difficile TcdC is a membrane-associated protein","volume":"188","author":"Govind","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4683","DOI":"10.1128\/AEM.00249-12","article-title":"Precise manipulation of the Clostridium difficile chromosome reveals a lack of association between the tcdC genotype and toxin production","volume":"78","author":"Cartman","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1128\/JCM.01599-06","article-title":"tcdC genotypes associated with severe TcdC truncation in an epidemic clone and other strains of Clostridium difficile","volume":"45","author":"Curry","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Murray, R., Boyd, D., Levett, P.N., Mulvey, M.R., and Alfa, M.J. (2009). Truncation in the tcdC region of the Clostridium difficile PathLoc of clinical isolates does not predict increased biological activity of Toxin B or Toxin A. BMC Infect. Dis., 9.","DOI":"10.1186\/1471-2334-9-103"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Carter, G.P., Douce, G.R., Govind, R., Howarth, P.M., Mackin, K.E., Spencer, J., Buckley, A.M., Antunes, A., Kotsanas, D., and Jenkin, G.A. (2011). The anti-sigma factor TcdC modulates hypervirulence in an epidemic BI\/NAP1\/027 clinical isolate of Clostridium difficile. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002317"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1128\/aem.61.6.2425-2427.1995","article-title":"Enhanced fermentation of mannitol and release of cytotoxin by Clostridium difficile in alkaline culture media","volume":"61","author":"Kazamias","year":"1995","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1128\/MMBR.00024-06","article-title":"How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria","volume":"70","author":"Deutscher","year":"2006","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1146\/annurev.micro.54.1.849","article-title":"Regulation of carbon catabolism in Bacillus species","volume":"54","author":"Stulke","year":"2000","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nature25178","article-title":"Dietary trehalose enhances virulence of epidemic Clostridium difficile","volume":"553","author":"Collins","year":"2018","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.mib.2005.01.001","article-title":"CodY, a global regulator of stationary phase and virulence in Gram-positive bacteria","volume":"8","author":"Sonenshein","year":"2005","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5350","DOI":"10.1128\/JB.00341-10","article-title":"Integration of metabolism and virulence by Clostridium difficile CodY","volume":"192","author":"Dineen","year":"2010","journal-title":"J. Bacteriol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s002840010164","article-title":"The rpoN gene of Enterococcus faecalis directs sensitivity to subclass IIa bacteriocins","volume":"41","author":"Dalet","year":"2000","journal-title":"Curr. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1574-6968.2006.00405.x","article-title":"The sigma factor RpoN (sigma54) is involved in osmotolerance in Listeria monocytogenes","volume":"263","author":"Okada","year":"2006","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3389\/fcimb.2017.00531","article-title":"Novel Cysteine Desulfidase CdsB Involved in Releasing Cysteine Repression of Toxin Synthesis in Clostridium difficile","volume":"7","author":"Gu","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1111\/mmi.14245","article-title":"Role of the global regulator Rex in control of NAD+ -regeneration in Clostridioides (Clostridium) difficile","volume":"111","author":"Bouillaut","year":"2019","journal-title":"Mol Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Martin-Verstraete, I., Peltier, J., and Dupuy, B. (2016). The Regulatory Networks That Control Clostridium difficile Toxin Synthesis. Toxins, 8.","DOI":"10.3390\/toxins8050153"},{"key":"ref_54","first-page":"1","article-title":"Regulatory transcription factors of Clostridioides difficile pathogenesis with a focus on toxin regulation","volume":"7","author":"Chandra","year":"2022","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Girinathan, P.B., Ou, J., Dupuy, B., and Govind, R. (2018). Pleiotropic roles of Clostridium difficile sin locus. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006940"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e00963-20","DOI":"10.1128\/mSphere.00963-20","article-title":"Spo0A Suppresses sin Locus Expression in Clostridioides difficile","volume":"5","author":"Dhungel","year":"2020","journal-title":"mSphere"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3186","DOI":"10.1128\/JB.00272-11","article-title":"The key sigma factor of transition phase, SigH, controls sporulation, metabolism, and virulence factor expression in Clostridium difficile","volume":"193","author":"Saujet","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1111\/mmi.13361","article-title":"A novel regulator controls Clostridium difficile sporulation, motility and toxin production","volume":"100","author":"Edwards","year":"2016","journal-title":"Mol. Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e01991-18","DOI":"10.1128\/mBio.01991-18","article-title":"RstA Is a major regulator of Clostridioides difficile toxin production and motility","volume":"10","author":"Edwards","year":"2019","journal-title":"mBio"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3672","DOI":"10.1128\/JB.00473-13","article-title":"The agr locus regulates virulence and colonization genes in Clostridium difficile 027","volume":"195","author":"Martin","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5174","DOI":"10.1128\/JB.00501-13","article-title":"The second messenger cyclic Di-GMP regulates Clostridium difficile toxin production by controlling expression of sigD","volume":"195","author":"McKee","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.bbrc.2005.07.131","article-title":"LuxS\/autoinducer-2 quorum sensing molecule regulates transcriptional virulence gene expression in Clostridium difficile","volume":"335","author":"Lee","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s00018-008-8378-6","article-title":"The bacterial LexA transcriptional repressor","volume":"66","author":"Butala","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1111\/j.1574-6976.2007.00082.x","article-title":"Aeons of distress: An evolutionary perspective on the bacterial SOS response","volume":"31","author":"Erill","year":"2007","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Walter, B.M., Cartman, S.T., Minton, N.P., Butala, M., and Rupnik, M. (2015). The SOS response master regulator LexA is associated with sporulation, motility and biofilm formation in Clostridium difficile. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144763"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Walter, B.M., Rupnik, M., Hodnik, V., Anderluh, G., Dupuy, B., Paulic, N., Zgur-Bertok, D., and Butala, M. (2014). The LexA regulated genes of the Clostridium difficile. BMC Microbiol., 14.","DOI":"10.1186\/1471-2180-14-88"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3757","DOI":"10.1128\/IAI.00515-13","article-title":"Adaptive strategies and pathogenesis of Clostridium difficile from in vivo transcriptomics","volume":"81","author":"Janoir","year":"2013","journal-title":"Infect. Immun."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/15\/7\/413\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:00:49Z","timestamp":1760126449000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/15\/7\/413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,26]]},"references-count":67,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["toxins15070413"],"URL":"https:\/\/doi.org\/10.3390\/toxins15070413","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,26]]}}}