{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T15:26:02Z","timestamp":1791127562082,"version":"4.1.0"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Botulinum neurotoxins (BoNTs) produced by\n            <jats:named-content content-type=\"genus-species\">Clostridium botulinum<\/jats:named-content>\n            are of considerable importance due to their being the cause of human and animal botulism, their potential as bioterrorism agents, and their utility as important pharmaceuticals. Type A is prominent due to its high toxicity and long duration of action. Five subtypes of type A BoNT are currently recognized; BoNT\/A1, -\/A2, and -\/A5 have been purified, and their properties have been studied. BoNT\/A3 is intriguing because it is not effectively neutralized by polyclonal anti-BoNT\/A1 antibodies, and thus, it may potentially replace BoNT\/A1 for patients who have become refractive to treatment with BoNT\/A1 due to antibody formation or other modes of resistance. Purification of BoNT\/A3 has been challenging because of its low levels of production in culture and the need for innovative purification procedures. In this study, modified Mueller-Miller medium was used in place of traditional toxin production medium (TPM) to culture\n            <jats:named-content content-type=\"genus-species\">C. botulinum<\/jats:named-content>\n            A3 (CDC strain) and boost toxin production. BoNT\/A3 titers were at least 10-fold higher than those produced in TPM. A purification method was developed to obtain greater than 95% pure BoNT\/A3. The specific toxicity of BoNT\/A3 as determined by mouse bioassay was 5.8 \u00d7 10\n            <jats:sup>7<\/jats:sup>\n            50% lethal doses (LD\n            <jats:sub>50<\/jats:sub>\n            )\/mg. Neutralization of BoNT\/A3 toxicity by a polyclonal anti-BoNT\/A1 antibody was approximately 10-fold less than the neutralization of BoNT\/A1 toxicity. In addition, differences in symptoms were observed between mice that were injected with BoNT\/A3 and those that were injected with BoNT\/A1. These results indicate that BoNT\/A3 has novel biochemical and pharmacological properties compared to those of other subtype A toxins.\n          <\/jats:p>","DOI":"10.1128\/aem.07967-11","type":"journal-article","created":{"date-parts":[[2012,2,25]],"date-time":"2012-02-25T05:29:55Z","timestamp":1330147795000},"page":"3108-3113","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Purification and Characterization of a Novel Subtype A3 Botulinum Neurotoxin"],"prefix":"10.1128","volume":"78","author":[{"given":"William H.","family":"Tepp","sequence":"first","affiliation":[{"name":"Department of Bacteriology, Food Research Institute, University of Wisconsin\u2014Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Food Research Institute, University of Wisconsin\u2014Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Food Research Institute, University of Wisconsin\u2014Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.8.1059"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1111\/j.1468-3083.2010.03631.x","article-title":"International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit)\u2014part I: upper facial wrinkles","volume":"24","author":"Ascher B","year":"2010","unstructured":"AscherB . 2010. International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit)\u2014part I: upper facial wrinkles. J. Eur. Acad. Dermatol. Venereol. 24:1278\u20131284.","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1111\/j.1468-3083.2010.03728.x","article-title":"International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit)\u2014part II: wrinkles on the middle and lower face, neck and chest","volume":"24","author":"Ascher B","year":"2010","unstructured":"AscherB . 2010. International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit)\u2014part II: wrinkles on the middle and lower face, neck and chest. J. Eur. Acad. Dermatol. Venereol. 24:1285\u20131295.","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)61557-1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)42071-0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-10-115"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0041-0101(84)90085-0"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00799-09"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9519009"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4612-3898-0_12"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3109\/15563650.2011.571694","article-title":"The ripe olive scare and Hotel Loch Maree tragedy: botulism under glass in the 1920's","volume":"49","author":"Horowitz BZ","year":"2011","unstructured":"HorowitzBZ. 2011. The ripe olive scare and Hotel Loch Maree tragedy: botulism under glass in the 1920's. Clin. Toxicol. 49:345\u2013347.","journal-title":"Clin. Toxicol."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02828-07"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00201-11"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2008\/016915-0"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.53.1.551"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2945"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/2338"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01882-09"},{"key":"e_1_3_2_21_2","first-page":"27","article-title":"Purification of Clostridium botulinum type A neurotoxin","volume":"145","author":"Malizio CJ","year":"2000","unstructured":"MalizioCJ GoodnoughMC JohnsonEA. 2000. Purification of Clostridium botulinum type A neurotoxin. Methods Mol. Biol. 145:27\u201339.","journal-title":"Methods Mol. Biol."},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.06.166"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"e12416","DOI":"10.1371\/journal.pone.0012416","article-title":"Characterization of botulinum neurotoxin type A neutralizing monoclonal antibodies and influence of their half-lives on therapeutic activity","volume":"5","author":"Mazuet C","year":"2010","unstructured":"MazuetC DanoJ PopoffMR CreminonC VollandH. 2010. Characterization of botulinum neurotoxin type A neutralizing monoclonal antibodies and influence of their half-lives on therapeutic activity. PLoS One 5:e12416.","journal-title":"PLoS One"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1172\/JCI101397","article-title":"Production of tetanus toxin on peptone-free media","volume":"22","author":"Mueller JH","year":"1943","unstructured":"MuellerJH SchoenbachEB JezukawiczJJ MillerPA. 1943. Production of tetanus toxin on peptone-free media. J. Clin. Invest. 22:315\u2013318.","journal-title":"J. Clin. Invest."},{"key":"e_1_3_2_25_2","first-page":"493","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed LJ","year":"1938","unstructured":"ReedLJ MuenchH. 1938. A simple method of estimating fifty percent endpoints. Am. J. Hyg. 27:493\u2013497.","journal-title":"Am. J. Hyg."},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)35863-0"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"10566","DOI":"10.1074\/jbc.270.18.10566","article-title":"Botulinum neurotoxin type C cleaves a single Lys-Ala bond within the carboxyl-terminal region of syntaxins","volume":"270","author":"Schiavo G","year":"1995","unstructured":"SchiavoG ShoneCC BennettMK SchellerRH MontecuccoC. 1995. Botulinum neurotoxin type C cleaves a single Lys-Ala bond within the carboxyl-terminal region of syntaxins. J. Biol. Chem. 270:10566\u201310570.","journal-title":"J. Biol. Chem."},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1177\/1759720X09357113","article-title":"Botulinum toxin therapy for osteoarticular pain: an evidence-based review","volume":"2","author":"Singh JA","year":"2010","unstructured":"SinghJA. 2010. Botulinum toxin therapy for osteoarticular pain: an evidence-based review. Ther. Adv. Musculoskelet. Dis. 2:105\u2013118.","journal-title":"Ther. Adv. Musculoskelet. Dis."},{"key":"e_1_3_2_29_2","volume-title":"The organism, its toxins, the disease","author":"Smith LDS","year":"1988","unstructured":"SmithLDS SugiyamaH. 1988. Botulism. The organism, its toxins, the disease. Charles C Thomas, Springfield, IL."},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1017\/S0022172400055911","article-title":"A comparison of the distribution of Clostridium botulinum in soil and in lake mud","volume":"78","author":"Smith GR","year":"1977","unstructured":"SmithGR MorysonCJ. 1977. A comparison of the distribution of Clostridium botulinum in soil and in lake mud. J. Hyg. (Lond.) 78:39\u201341.","journal-title":"J. Hyg. (Lond.)"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001271"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.05.030"}],"container-title":["Applied and Environmental Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AEM.07967-11","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AEM.07967-11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T19:47:55Z","timestamp":1645645675000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AEM.07967-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5]]},"references-count":30,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2012,5]]}},"alternative-id":["10.1128\/AEM.07967-11"],"URL":"https:\/\/doi.org\/10.1128\/aem.07967-11","relation":{},"ISSN":["0099-2240","1098-5336"],"issn-type":[{"value":"0099-2240","type":"print"},{"value":"1098-5336","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5]]},"assertion":[{"value":"2011-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-02-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-04-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}