{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T02:25:56Z","timestamp":1773195956256,"version":"3.50.1"},"reference-count":148,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T00:00:00Z","timestamp":1525910400000},"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>Botulinum neurotoxins (BoNTs), the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now \u201cbooming field\u201d of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.<\/jats:p>","DOI":"10.3390\/toxins10050190","type":"journal-article","created":{"date-parts":[[2018,5,11]],"date-time":"2018-05-11T03:42:48Z","timestamp":1526010168000},"page":"190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Novel Botulinum Neurotoxins: Exploring Underneath the Iceberg Tip"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-7240","authenticated-orcid":false,"given":"Domenico","family":"Azarnia Tehran","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, Via Ugo Bassi 58\/B, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4127-254X","authenticated-orcid":false,"given":"Marco","family":"Pirazzini","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, Via Ugo Bassi 58\/B, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1124\/pr.116.012658","article-title":"Botulinum neurotoxins: Biology, pharmacology, and toxicology","volume":"69","author":"Pirazzini","year":"2017","journal-title":"Pharmacol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/nrmicro3295","article-title":"Botulinum neurotoxins: Genetic, structural and mechanistic insights","volume":"12","author":"Rossetto","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0072-9752(07)01511-4","article-title":"Botulism","volume":"91","author":"Johnson","year":"2008","journal-title":"Handb. Clin. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/26412","article-title":"Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 a resolution","volume":"395","author":"Sutton","year":"1998","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"S\u00fcdhof, T.C., and Rizo, J. (2011). Synaptic vesicle exocytosis. Cold Spring Harb. Perspect. Biol., 3.","DOI":"10.1101\/cshperspect.a005637"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1152\/physrev.2000.80.2.717","article-title":"Neurotoxins affecting neuroexocytosis","volume":"80","author":"Schiavo","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.toxicon.2012.12.004","article-title":"Evidence-based review and assessment of botulinum neurotoxin for the treatment of movement disorders","volume":"67","author":"Hallett","year":"2013","journal-title":"Toxicon"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.toxicon.2012.10.020","article-title":"Evidence-based review and assessment of botulinum neurotoxin for the treatment of secretory disorders","volume":"67","author":"Naumann","year":"2013","journal-title":"Toxicon"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/mds.27072","article-title":"Botulinum toxin: State of the art","volume":"32","author":"Jankovic","year":"2017","journal-title":"Mov. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0041-0101(00)00163-X","article-title":"Tetanus and botulinum neurotoxins: Turning bad guys into good by research","volume":"39","author":"Rossetto","year":"2001","journal-title":"Toxicon"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Caleo, M., and Restani, L. (2018). Exploiting botulinum neurotoxins for the study of brain physiology and pathology. Toxins, 10.","DOI":"10.3390\/toxins10050175"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12676","DOI":"10.1002\/anie.201402380","article-title":"The principle of membrane fusion in the cell (nobel lecture)","volume":"53","author":"Rothman","year":"2014","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1001\/jama.285.8.1059","article-title":"Botulinum toxin as a biological weapon: Medical and public health management","volume":"285","author":"Arnon","year":"2001","journal-title":"JAMA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.resmic.2014.09.007","article-title":"Historical and current perspectives on clostridium botulinum diversity","volume":"166","author":"Smith","year":"2015","journal-title":"Res. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Peck, M.W., Smith, T.J., Anniballi, F., Austin, J.W., Bano, L., Bradshaw, M., Cuervo, P., Cheng, L.W., Derman, Y., and Dorner, B.G. (2017). Historical perspectives and guidelines for botulinum neurotoxin subtype nomenclature. Toxins, 9.","DOI":"10.3390\/toxins9010038"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e02131-14","DOI":"10.1128\/mBio.02131-14","article-title":"On botulinum neurotoxin variability","volume":"6","author":"Montecucco","year":"2015","journal-title":"MBio"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mansfield, M.J., and Doxey, A.C. (2018). Genomic insights into the evolution and ecology of botulinum neurotoxins. Pathog. Dis.","DOI":"10.1093\/femspd\/fty040"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.toxicon.2018.02.002","article-title":"Discovery of novel bacterial toxins by genomics and computational biology","volume":"147","author":"Doxey","year":"2018","journal-title":"Toxicon"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/2338","article-title":"Crystal structure of botulinum neurotoxin type a and implications for toxicity","volume":"5","author":"Lacy","year":"1998","journal-title":"Nat. Struct. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/78005","article-title":"Structural analysis of the catalytic and binding sites of clostridium botulinum neurotoxin b","volume":"7","author":"Swaminathan","year":"2000","journal-title":"Nat. Struct. Biol."},{"key":"ref_21","first-page":"1","article-title":"Two feet on the membrane: Uptake of clostridial neurotoxins","volume":"406","author":"Rummel","year":"2016","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1111\/j.1471-4159.2009.06093.x","article-title":"Cell entry strategy of clostridial neurotoxins","volume":"109","author":"Binz","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.bbrc.2009.01.037","article-title":"The n-terminal half of the receptor domain of botulinum neurotoxin a binds to microdomains of the plasma membrane","volume":"380","author":"Muraro","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.biochi.2011.11.004","article-title":"The receptor binding domain of botulinum neurotoxin serotype c binds phosphoinositides","volume":"94","author":"Zhang","year":"2012","journal-title":"Biochimie"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/nsmb.3245","article-title":"N-linked glycosylation of SV2 is required for binding and uptake of botulinum neurotoxin A","volume":"23","author":"Yao","year":"2016","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/nsmb.3253","article-title":"Botulinum neurotoxin a1 likes it double sweet","volume":"23","author":"Montecucco","year":"2016","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.toxicon.2013.01.007","article-title":"Molecular dissection of botulinum neurotoxin reveals interdomain chaperone function","volume":"75","author":"Fischer","year":"2013","journal-title":"Toxicon"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1146\/annurev.biochem.051908.125345","article-title":"Botulinum neurotoxin: A marvel of protein design","volume":"79","author":"Montal","year":"2010","journal-title":"Annu. Rev. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.bbamem.2015.08.014","article-title":"On the translocation of botulinum and tetanus neurotoxins across the membrane of acidic intracellular compartments","volume":"1858","author":"Pirazzini","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00018-013-1380-7","article-title":"The blockade of the neurotransmitter release apparatus by botulinum neurotoxins","volume":"71","author":"Pantano","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_31","first-page":"139","article-title":"Clostridial neurotoxin light chains: Devices for SNARE cleavage mediated blockade of neurotransmission","volume":"364","author":"Binz","year":"2013","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"23479","DOI":"10.1016\/S0021-9258(18)35863-0","article-title":"Botulinum neurotoxins are zinc proteins","volume":"267","author":"Schiavo","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.toxicon.2013.02.014","article-title":"The life history of a botulinum toxin molecule","volume":"68","author":"Simpson","year":"2013","journal-title":"Toxicon"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1080\/17460441.2017.1303476","article-title":"Challenges in searching for therapeutics against botulinum neurotoxins","volume":"12","author":"Pirazzini","year":"2017","journal-title":"Exp. Opin. Drug Discov."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.toxicon.2017.10.028","article-title":"Hsp90 and thioredoxin-thioredoxin reductase enable the catalytic activity of clostridial neurotoxins inside nerve terminals","volume":"147","author":"Pirazzini","year":"2017","journal-title":"Toxicon"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.toxicon.2015.06.019","article-title":"The thioredoxin reductase\u2014Thioredoxin redox system cleaves the interchain disulphide bond of botulinum neurotoxins on the cytosolic surface of synaptic vesicles","volume":"107","author":"Pirazzini","year":"2015","journal-title":"Toxicon"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/0968-0004(86)90282-3","article-title":"How do tetanus and botulinum toxins bind to neuronal membranes?","volume":"11","author":"Montecucco","year":"1986","journal-title":"Trends Biochem. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature12732","article-title":"Structural basis for recognition of synaptic vesicle protein 2c by botulinum neurotoxin a","volume":"505","author":"Benoit","year":"2014","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.tibs.2014.08.009","article-title":"Botulinum neurotoxins: New questions arising from structural biology","volume":"39","author":"Kammerer","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1126\/science.1123654","article-title":"SV2 is the protein receptor for botulinum neurotoxin a","volume":"312","author":"Dong","year":"2006","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5226","DOI":"10.1091\/mbc.e08-07-0765","article-title":"Glycosylated SV2A and SV2B mediate the entry of botulinum neurotoxin e into neurons","volume":"19","author":"Dong","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10498","DOI":"10.1016\/S0021-9258(17)34087-5","article-title":"Identification of protein receptor for clostridium botulinum type b neurotoxin in rat brain synaptosomes","volume":"269","author":"Nishiki","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_43","first-page":"3233","article-title":"Botulinum neurotoxin d-c uses synaptotagmin i and ii as receptors, and human synaptotagmin ii is not an effective receptor for type b, d-c and g toxins","volume":"125","author":"Peng","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"30865","DOI":"10.1074\/jbc.M403945200","article-title":"Synaptotagmins i and ii act as nerve cell receptors for botulinum neurotoxin g","volume":"279","author":"Rummel","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1042\/BCJ20160439","article-title":"Only the complex n559-glycan in the synaptic vesicle glycoprotein 2c mediates high affinity binding to botulinum neurotoxin serotype a1","volume":"473","author":"Mahrhold","year":"2016","journal-title":"Biochem. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1093\/glycob\/cwq052","article-title":"Common aberrations from the normal human plasma n-glycan profile","volume":"20","author":"Pucic","year":"2010","journal-title":"Glycobiology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1021\/pr800737u","article-title":"Variability, heritability and environmental determinants of human plasma n-glycome","volume":"8","author":"Knezevic","year":"2009","journal-title":"J. Proteom. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1016\/j.bbagen.2015.10.016","article-title":"Mechanisms of disease: The human n-glycome","volume":"1860","author":"Lauc","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1038\/s41467-017-01534-z","article-title":"Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin dc","volume":"8","author":"Zhang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.vetmic.2009.07.023","article-title":"Characterization of the d\/c mosaic neurotoxin produced by clostridium botulinum associated with bovine botulism in Japan","volume":"140","author":"Nakamura","year":"2010","journal-title":"Vet. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"26828","DOI":"10.1074\/jbc.M111.254086","article-title":"Novel ganglioside-mediated entry of botulinum neurotoxin serotype d into neurons","volume":"286","author":"Kroken","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Peng, L., Tepp, W.H., Johnson, E.A., and Dong, M. (2011). Botulinum neurotoxin d uses synaptic vesicle protein SV2 and gangliosides as receptors. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002008"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1042\/BJ20101042","article-title":"Botulinum neurotoxin serotype d attacks neurons via two carbohydrate-binding sites in a ganglioside-dependent manner","volume":"431","author":"Strotmeier","year":"2010","journal-title":"Biochem. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"35164","DOI":"10.1074\/jbc.M507596200","article-title":"Binding of clostridium botulinum type c and d neurotoxins to ganglioside and phospholipid. Novel insights into the receptor for clostridial neurotoxins","volume":"280","author":"Tsukamoto","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4486","DOI":"10.1111\/j.1742-4658.2011.08166.x","article-title":"Unique ganglioside binding by botulinum neurotoxins c and d-sa","volume":"278","author":"Kroken","year":"2011","journal-title":"FEBS J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8117","DOI":"10.1021\/bi100865f","article-title":"Identification of a unique ganglioside binding loop within botulinum neurotoxins c and d-sa","volume":"49","author":"Karalewitz","year":"2010","journal-title":"Biochemistry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s12035-013-8423-9","article-title":"Botulinum neurotoxin type a is internalized and translocated from small synaptic vesicles at the neuromuscular junction","volume":"48","author":"Colasante","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"19654","DOI":"10.1038\/srep19654","article-title":"Botulinum neurotoxin type-a enters a non-recycling pool of synaptic vesicles","volume":"6","author":"Harper","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"35966","DOI":"10.1074\/jbc.M111.283879","article-title":"Dynamin inhibition blocks botulinum neurotoxin type a endocytosis in neurons and delays botulism","volume":"286","author":"Harper","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nsb879","article-title":"Translocation of botulinum neurotoxin light chain protease through the heavy chain channel","volume":"10","author":"Koriazova","year":"2003","journal-title":"Nat. Struct. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1111\/j.1462-5822.2011.01654.x","article-title":"Double anchorage to the membrane and intact inter-chain disulfide bond are required for the low ph induced entry of tetanus and botulinum neurotoxins into neurons","volume":"13","author":"Pirazzini","year":"2011","journal-title":"Cell. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.chom.2011.06.012","article-title":"Receptor binding enables botulinum neurotoxin b to sense low ph for translocation channel assembly","volume":"10","author":"Sun","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"29604","DOI":"10.1074\/jbc.M703619200","article-title":"Crucial role of the disulfide bridge between botulinum neurotoxin light and heavy chains in protease translocation across membranes","volume":"282","author":"Fischer","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Azarnia Tehran, D., Pirazzini, M., Leka, O., Mattarei, A., Lista, F., Binz, T., Rossetto, O., and Montecucco, C. (2017). Hsp90 is involved in the entry of clostridial neurotoxins into the cytosol of nerve terminals. Cell. Microbiol., 19.","DOI":"10.1111\/cmi.12647"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.bcp.2015.09.023","article-title":"Inhibition of botulinum neurotoxins interchain disulfide bond reduction prevents the peripheral neuroparalysis of botulism","volume":"98","author":"Zanetti","year":"2015","journal-title":"Biochem. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.clinph.2012.11.004","article-title":"Botulinum neurotoxin serotype d is poorly effective in humans: An in vivo electrophysiological study","volume":"124","author":"Eleopra","year":"2013","journal-title":"Clin. Neurophysiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF02220526","article-title":"Ueber einen neuen ana\u00ebroben bacillus und seine beziehungen zum botulismus","volume":"26","year":"1897","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1002\/mds.20003","article-title":"Historical notes on botulism, clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin","volume":"19","author":"Erbguth","year":"2004","journal-title":"Mov. Disord."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1128\/aem.62.2.662-667.1996","article-title":"Molecular cloning of the gene encoding the mosaic neurotoxin, composed of parts of botulinum neurotoxin types c1 and d, and pcr detection of this gene from clostridium botulinum type c organisms","volume":"62","author":"Moriishi","year":"1996","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0167-4781(96)00006-1","article-title":"Mosaic structures of neurotoxins produced from clostridium botulinum types c and d organisms","volume":"1307","author":"Moriishi","year":"1996","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1099\/jmm.0.031179-0","article-title":"Confirmation of botulism in birds and cattle by the mouse bioassay and endopep-ms","volume":"60","author":"Hedeland","year":"2011","journal-title":"J. Med. Microbiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.vetmic.2012.11.009","article-title":"Improved detection methods by genetic and immunological techniques for botulinum c\/d and d\/c mosaic neurotoxins","volume":"162","author":"Nakamura","year":"2013","journal-title":"Vet. Microbiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1637\/7347-022305R1.1","article-title":"Characterization of the neurotoxin produced by isolates associated with avian botulism","volume":"49","author":"Takeda","year":"2005","journal-title":"Avian Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"757","DOI":"10.3389\/fmicb.2016.00757","article-title":"New insights into the genetic diversity of clostridium botulinum group iii through extensive genome exploration","volume":"7","author":"Woudstra","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Williamson, C.H., Sahl, J.W., Smith, T.J., Xie, G., Foley, B.T., Smith, L.A., Fernandez, R.A., Lindstrom, M., Korkeala, H., and Keim, P. (2016). Comparative genomic analyses reveal broad diversity in botulinum-toxin-producing clostridia. BMC Genom., 17.","DOI":"10.1186\/s12864-016-2502-z"},{"key":"ref_76","first-page":"1","article-title":"Genetic diversity within clostridium botulinum serotypes, botulinum neurotoxin gene clusters and toxin subtypes","volume":"364","author":"Hill","year":"2013","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1128\/JB.01180-06","article-title":"Genetic diversity among botulinum neurotoxin-producing clostridial strains","volume":"189","author":"Hill","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.meegid.2015.08.042","article-title":"Genomic characterization of italian clostridium botulinum group i strains","volume":"36","author":"Giordani","year":"2015","journal-title":"Infect. Genet. Evol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4252","DOI":"10.1128\/JCM.05396-11","article-title":"Clostridium botulinum group i strain genotyping by 15-locus multilocus variable-number tandem-repeat analysis","volume":"49","author":"Fillo","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Whitemarsh, R.C., Tepp, W.H., Johnson, E.A., and Pellett, S. (2014). Persistence of botulinum neurotoxin a subtypes 1-5 in primary rat spinal cord cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090252"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1016\/j.bbapap.2013.09.007","article-title":"Comparison of the catalytic properties of the botulinum neurotoxin subtypes a1 and a5","volume":"1834","author":"Wang","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3894","DOI":"10.1128\/IAI.00536-13","article-title":"Characterization of botulinum neurotoxin a subtypes 1 through 5 by investigation of activities in mice, in neuronal cell cultures, and in vitro","volume":"81","author":"Whitemarsh","year":"2013","journal-title":"Infect. Immun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.febslet.2010.11.045","article-title":"Botulinum neurotoxin subtype a2 enters neuronal cells faster than subtype a1","volume":"585","author":"Pier","year":"2011","journal-title":"FEBS Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.toxicon.2015.06.021","article-title":"In vivo onset and duration of action varies for botulinum neurotoxin a subtypes 1-5","volume":"107","author":"Pellett","year":"2015","journal-title":"Toxicon"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1111\/bcpt.12351","article-title":"Comparison of systemic toxicity between botulinum toxin subtypes a1 and a2 in mice and rats","volume":"116","author":"Torii","year":"2015","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Kull, S., Schulz, K.M., Weisemann, J., Kirchner, S., Schreiber, T., Bollenbach, A., Dabrowski, P.W., Nitsche, A., Kalb, S.R., and Dorner, M.B. (2015). Isolation and functional characterization of the novel clostridium botulinum neurotoxin a8 subtype. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116381"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.febslet.2011.11.033","article-title":"Discovery of a novel enzymatic cleavage site for botulinum neurotoxin f5","volume":"586","author":"Kalb","year":"2012","journal-title":"FEBS Lett."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4811","DOI":"10.1128\/IAI.66.10.4811-4816.1998","article-title":"Characterization of clostridium botulinum type b neurotoxin associated with infant botulism in japan","volume":"66","author":"Kozaki","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.toxicon.2015.08.001","article-title":"Clinical differences between botulinum neurotoxin type a and b","volume":"107","author":"Bentivoglio","year":"2015","journal-title":"Toxicon"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"13493","DOI":"10.1523\/JNEUROSCI.3519-06.2006","article-title":"Synaptotagmin-2 is essential for survival and contributes to Ca2+ triggering of neurotransmitter release in central and neuromuscular synapses","volume":"26","author":"Pang","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/0306-4522(94)90528-2","article-title":"Synaptotagmin i is present mainly in autonomic and sensory neurons of the rat peripheral nervous system","volume":"63","author":"Li","year":"1994","journal-title":"Neuroscience"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1021\/bi200290p","article-title":"Syntaxin requirement for Ca2+-triggered exocytosis in neurons and endocrine cells demonstrated with an engineered neurotoxin","volume":"50","author":"Wang","year":"2011","journal-title":"Biochemistry"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zanetti, G., Sikorra, S., Rummel, A., Krez, N., Duregotti, E., Negro, S., Henke, T., Rossetto, O., Binz, T., and Pirazzini, M. (2017). Botulinum neurotoxin c mutants reveal different effects of syntaxin or snap-25 proteolysis on neuromuscular transmission. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006567"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1093\/infdis\/jit450","article-title":"Molecular characterization of a novel botulinum neurotoxin type h gene","volume":"209","author":"Dover","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1093\/infdis\/jit449","article-title":"A novel strain of clostridium botulinum that produces type b and type h botulinum toxins","volume":"209","author":"Barash","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1093\/infdis\/jiu211","article-title":"Validity of botulinum neurotoxin serotype h","volume":"210","author":"Johnson","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1093\/infdis\/jiv327","article-title":"A novel botulinum neurotoxin, previously reported as serotype h, has a hybrid-like structure with regions of similarity to the structures of serotypes a and f and is neutralized with serotype a antitoxin","volume":"213","author":"Maslanka","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3911","DOI":"10.1021\/ac504716v","article-title":"Functional characterization of botulinum neurotoxin serotype h as a hybrid of known serotypes f and a (bont f\/a)","volume":"87","author":"Kalb","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Yao, G., Lam, K., Perry, K., Weisemann, J., Rummel, A., and Jin, R. (2017). Crystal structure of the receptor-binding domain of botulinum neurotoxin type ha, also known as type fa or h. Toxins, 9.","DOI":"10.2210\/pdb5v38\/pdb"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1093\/infdis\/jiv770","article-title":"Immunological characterization and neutralizing ability of monoclonal antibodies directed against botulinum neurotoxin type h","volume":"213","author":"Fan","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e00100-15","DOI":"10.1128\/mSphere.00100-15","article-title":"Purification and characterization of botulinum neurotoxin fa from a genetically modified clostridium botulinum strain","volume":"1","author":"Pellett","year":"2016","journal-title":"mSphere"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.toxicon.2017.12.048","article-title":"Substrate cleavage and duration of action of botulinum neurotoxin type fa (\u201ch, ha\u201d)","volume":"147","author":"Pellett","year":"2018","journal-title":"Toxicon"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/j.1442-200X.1996.tb03542.x","article-title":"The first case of type b infant botulism in japan","volume":"38","author":"Kakinuma","year":"1996","journal-title":"Pediatr. Int."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/j.1348-0421.2012.00441.x","article-title":"Stability of toxigenicity in proteolytic clostridium botulinum type b upon serial passage","volume":"56","author":"Umeda","year":"2012","journal-title":"Microbiol. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"14130","DOI":"10.1038\/ncomms14130","article-title":"Identification and characterization of a novel botulinum neurotoxin","volume":"8","author":"Zhang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"20353","DOI":"10.1074\/jbc.271.34.20353","article-title":"Structural determinants of the specificity for synaptic vesicle-associated membrane protein\/synaptobrevin of tetanus and botulinum type b and g neurotoxins","volume":"271","author":"Pellizzari","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/372415a0","article-title":"SNARE motif and neurotoxins","volume":"372","author":"Rossetto","year":"1994","journal-title":"Nature"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/nature03123","article-title":"Substrate recognition strategy for botulinum neurotoxin serotype a","volume":"432","author":"Breidenbach","year":"2004","journal-title":"Nature"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/nsmb.1626","article-title":"Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin f","volume":"16","author":"Agarwal","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4518","DOI":"10.1038\/s41598-018-22842-4","article-title":"Structural characterisation of the catalytic domain of botulinum neurotoxin x\u2014High activity and unique substrate specificity","volume":"8","author":"Masuyer","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.febslet.2014.12.018","article-title":"Botulinum neurotoxin homologs in non-clostridium species","volume":"589","author":"Mansfield","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4613","DOI":"10.1099\/ijs.0.053124-0","article-title":"Lactobacillus silagei sp. nov., isolated from orchardgrass silage","volume":"63","author":"Tohno","year":"2013","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1006\/bbrc.2001.5911","article-title":"Site-directed mutagenesis identifies active-site residues of the light chain of botulinum neurotoxin type a","volume":"288","author":"Rigoni","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"30257","DOI":"10.1038\/srep30257","article-title":"The first non clostridial botulinum-like toxin cleaves VAMP within the juxtamembrane domain","volume":"6","author":"Zornetta","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"8378","DOI":"10.1073\/pnas.0602644103","article-title":"Conformation of the synaptobrevin transmembrane domain","volume":"103","author":"Bowen","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.febslet.2012.11.002","article-title":"Juxtamembrane tryptophans of synaptobrevin 2 control the process of membrane fusion","volume":"587","author":"Fang","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/1873-3468.12969","article-title":"Identification of a novel botulinum neurotoxin gene cluster in enterococcus","volume":"592","author":"Brunt","year":"2018","journal-title":"FEBS Lett."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Williamson, C.H.D., Smith, T.J., Foley, B.T., Hill, K., Keim, P., and Sahl, J.W. (2017). Botulinum-neurotoxin-like sequences identified from an Enterococcus sp. Genome assembly. bioRxiv.","DOI":"10.1101\/228098"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.chom.2017.12.018","article-title":"Identification of a botulinum neurotoxin-like toxin in a commensal strain of enterococcus faecium","volume":"23","author":"Zhang","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_120","first-page":"924","article-title":"Pharmacologic weakening of extraocular muscles","volume":"12","author":"Scott","year":"1973","journal-title":"Investig. Ophthalmol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/S0161-6420(80)35127-0","article-title":"Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery","volume":"87","author":"Scott","year":"1980","journal-title":"Ophthalmology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/BF03033930","article-title":"Clinical use of non-a botulinum toxins: Botulinum toxin type c and botulinum toxin type f","volume":"9","author":"Eleopra","year":"2006","journal-title":"Neurotox. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1002\/mds.20010","article-title":"Different types of botulinum toxin in humans","volume":"19","author":"Eleopra","year":"2004","journal-title":"Mov. Disord."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0304-3940(98)00775-7","article-title":"Different time courses of recovery after poisoning with botulinum neurotoxin serotypes a and e in humans","volume":"256","author":"Eleopra","year":"1998","journal-title":"Neurosci. Lett."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0304-3940(97)13448-6","article-title":"Botulinum neurotoxin serotype c: A novel effective botulinum toxin therapy in human","volume":"224","author":"Eleopra","year":"1997","journal-title":"Neurosci. Lett."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Peng, L., Adler, M., Demogines, A., Borrell, A., Liu, H., Tao, L., Tepp, W.H., Zhang, S.-C., Johnson, E.A., and Sawyer, S.L. (2014). Widespread sequence variations in VAMP1 across vertebrates suggest a potential selective pressure from botulinum neurotoxins. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004177"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1348-0421.2012.00434.x","article-title":"Specificity of botulinum protease for human VAMP family proteins","volume":"56","author":"Yamamoto","year":"2012","journal-title":"Microbiol. Immunol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/S0022-3565(24)36519-X","article-title":"In vitro characterization of botulinum toxin types a, c and d action on human tissues: Combined electrophysiologic, pharmacologic and molecular biologic approaches","volume":"280","author":"Coffield","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.toxicon.2015.04.015","article-title":"Activity of botulinum neurotoxin type d (strain 1873) in human neurons","volume":"101","author":"Pellett","year":"2015","journal-title":"Toxicon"},{"key":"ref_130","unstructured":"Gupta, R.C. (2009). Chapter 30\u2014Botulinum toxin. Handbook of Toxicology of Chemical Warfare Agents, Academic Press."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Carle, S., Pirazzini, M., Rossetto, O., Barth, H., and Montecucco, C. (2017). High conservation of tetanus and botulinum neurotoxins cleavage sites on human SNARE proteins suggests that these pathogens exerted little or no evolutionary pressure on humans. Toxins, 9.","DOI":"10.3390\/toxins9120404"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1146\/annurev-pharmtox-011613-135935","article-title":"Engineered botulinum neurotoxins as new therapeutics","volume":"54","author":"Masuyer","year":"2014","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.jmb.2015.10.024","article-title":"Identification and characterization of botulinum neurotoxin a substrate binding pockets and their re-engineering for human snap-23","volume":"428","author":"Sikorra","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"9180","DOI":"10.1073\/pnas.0903111106","article-title":"Engineering botulinum neurotoxin to extend therapeutic intervention","volume":"106","author":"Chen","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"16993","DOI":"10.1074\/jbc.M710442200","article-title":"Novel chimeras of botulinum neurotoxins a and e unveil contributions from the binding, translocation, and protease domains to their functional characteristics","volume":"283","author":"Wang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1042\/BJ20120100","article-title":"Longer-acting and highly potent chimaeric inhibitors of excessive exocytosis created with domains from botulinum neurotoxin A and B","volume":"444","author":"Wang","year":"2012","journal-title":"Biochem. J."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuro.2016.12.008","article-title":"Bont\/ab hybrid maintains similar duration of paresis as bont\/a wild-type in murine running wheel assay","volume":"59","author":"Kutschenko","year":"2017","journal-title":"NeuroToxicology"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"3831","DOI":"10.1016\/j.febslet.2013.10.010","article-title":"Neutralisation of specific surface carboxylates speeds up translocation of botulinum neurotoxin type b enzymatic domain","volume":"587","author":"Pirazzini","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41467-017-00064-y","article-title":"Engineered botulinum neurotoxin b with improved efficacy for targeting human receptors","volume":"8","author":"Tao","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1111\/j.1471-4159.2004.02844.x","article-title":"Botulinum neurotoxin type d enables cytosolic delivery of enzymatically active cargo proteins to neurones via unfolded translocation intermediates","volume":"91","author":"Bade","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"13397","DOI":"10.1038\/srep13397","article-title":"Structural analysis of clostridium botulinum neurotoxin type d as a platform for the development of targeted secretion inhibitors","volume":"5","author":"Masuyer","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"42923","DOI":"10.1038\/srep42923","article-title":"Engineering botulinum neurotoxin c1 as a molecular vehicle for intra-neuronal drug delivery","volume":"7","author":"Beske","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/gt.2011.8","article-title":"Innocuous full-length botulinum neurotoxin targets and promotes the expression of lentiviral vectors in central and autonomic neurons","volume":"18","author":"Ovsepian","year":"2011","journal-title":"Gene Ther."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1021\/acs.bioconjchem.7b00157","article-title":"Conjugate of an igg binding domain with botulinum neurotoxin a lacking the acceptor moiety targets its SNARE protease into trka-expressing cells when coupled to anti-trka igg or fc-\u03b2ngf","volume":"28","author":"Nugent","year":"2017","journal-title":"Bioconjug. Chem."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3390\/toxins3040345","article-title":"Re-assembled botulinum neurotoxin inhibits cns functions without systemic toxicity","volume":"3","author":"Ferrari","year":"2011","journal-title":"Toxins"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"18197","DOI":"10.1073\/pnas.1007125107","article-title":"Snare tagging allows stepwise assembly of a multimodular medicinal toxin","volume":"107","author":"Darios","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e01296-17","DOI":"10.1128\/genomeA.01296-17","article-title":"Closed genome sequence of Chryseobacterium piperi strain CTM(T)\/ATCC BAA-1782, a gram-negative bacterium with clostridial neurotoxin-like coding sequences","volume":"5","author":"Wentz","year":"2017","journal-title":"Genome Announc."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Mansfield, M.J., Wentz, T.G., Zhang, S., Lee, E.J., Dong, M., Sharma, S.K., and Doxey, A.C. (2017). Newly identified relatives of botulinum neurotoxins shed light on their molecular evolution. bioRxiv.","DOI":"10.1101\/220806"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/10\/5\/190\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:04:05Z","timestamp":1760195045000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/10\/5\/190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,10]]},"references-count":148,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,5]]}},"alternative-id":["toxins10050190"],"URL":"https:\/\/doi.org\/10.3390\/toxins10050190","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,10]]}}}