Clostridium botulinum

C. botulinum is a Gram-positive, rod-shaped, spore-forming bacterium. It is an obligate anaerobe, requiring an environment that lacks oxygen. However, C. botulinum tolerates traces of oxygen due to the enzyme superoxide dismutase, which is an important antioxidant defense in nearly all cells exposed to oxygen.{{cite book | vauthors = Doyle MP | title = Food Microbiology: Fundamentals and Frontiers | publisher = ASM Press| year = 2007 | isbn = 978-1-55581-208-9}} C. botulinum is able to produce the neurotoxin only during sporulation, which can happen only in an anaerobic environment.

C. botulinum is divided into four distinct phenotypic groups (I-IV) and is also classified into seven serotypes (A–G) based on the antigenicity of the botulinum toxin produced.{{cite journal | vauthors = Peck MW, Stringer SC, Carter AT | title = Clostridium botulinum in the post-genomic era | journal = Food Microbiology | volume = 28 | issue = 2 | pages = 183–191 | date = April 2011 | pmid = 21315972 | doi = 10.1016/j.fm.2010.03.005 }}{{cite journal | vauthors = Shukla HD, Sharma SK | title = Clostridium botulinum: a bug with beauty and weapon | journal = Critical Reviews in Microbiology | volume = 31 | issue = 1 | pages = 11–18 | year = 2005 | pmid = 15839401 | doi = 10.1080/10408410590912952 | s2cid = 2855356 }} On the level visible to DNA sequences, the phenotypic grouping matches the results of whole-genome and rRNA analyses, and setotype grouping approximates the result of analyses focused specifically on the toxin sequence. The two phylogenetic trees do not match because of the ability of the toxin gene cluster to be horizontally transferred.{{cite book | vauthors = Hill KK, Smith TJ |chapter=Genetic Diversity Within Clostridium botulinum Serotypes, Botulinum Neurotoxin Gene Clusters and Toxin Subtypes |title=Botulinum Neurotoxins |series=Current Topics in Microbiology and Immunology |date=2012 |volume=364 |pages=1–20 |doi=10.1007/978-3-642-33570-9_1|pmid=23239346 |isbn=978-3-642-33569-3 |url=https://www.researchgate.net/publication/233914979}}

{{Main|Botulinum toxin}}

Botulinum neurotoxin (BoNT) production is the unifying feature of the species. Seven serotypes of toxins have been identified that are allocated a letter (A–G), several of which can cause disease in humans. They are resistant to degradation by enzymes found in the gastrointestinal tract. This allows for ingested toxins to be absorbed from the intestines into the bloodstream. Toxins can be further differentiated into subtypes on the bases of smaller variations.{{cite journal | vauthors = Peck MW, Smith TJ, Anniballi F, Austin JW, Bano L, Bradshaw M, Cuervo P, Cheng LW, Derman Y, Dorner BG, Fisher A, Hill KK, Kalb SR, Korkeala H, Lindström M, Lista F, Lúquez C, Mazuet C, Pirazzini M, Popoff MR, Rossetto O, Rummel A, Sesardic D, Singh BR, Stringer SC | title = Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature | journal = Toxins | volume = 9 | issue = 1 | page = 38 | date = January 2017 | pmid = 28106761 | pmc = 5308270 | doi = 10.3390/toxins9010038 | doi-access = free }}

However, all types of botulinum toxin are rapidly destroyed by heating to 100 °C for 15 minutes (900 seconds). 80 °C for 30 minutes also destroys BoNT.{{cite journal | doi = 10.1007/BF00395840 | vauthors = Notermans S, Havellar AH | year = 1980 | title = Removal and inactivation of botulinum toxin during production of drinking water from surface water | journal = Antonie van Leeuwenhoek | volume = 46 | issue = 5| pages = 511–514 | s2cid = 21102990}}{{cite journal | vauthors = Montecucco C, Molgó J | title = Botulinal neurotoxins: revival of an old killer | journal = Current Opinion in Pharmacology | volume = 5 | issue = 3 | pages = 274–279 | date = June 2005 | pmid = 15907915 | doi = 10.1016/j.coph.2004.12.006 }}

Most strains produce one type of BoNT, but strains producing multiple toxins have been described. C. botulinum producing B and F toxin types have been isolated from human botulism cases in New Mexico and California.{{cite journal | vauthors = Hatheway CL, McCroskey LM | title = Examination of feces and serum for diagnosis of infant botulism in 336 patients | journal = Journal of Clinical Microbiology | volume = 25 | issue = 12 | pages = 2334–2338 | date = December 1987 | pmid = 3323228 | pmc = 269483 | doi = 10.1128/JCM.25.12.2334-2338.1987 }} The toxin type has been designated Bf as the type B toxin was found in excess to the type F. Similarly, strains producing Ab and Af toxins have been reported.

Evidence indicates the neurotoxin genes have been the subject of horizontal gene transfer, possibly from a viral (bacteriophage) source. This theory is supported by the presence of integration sites flanking the toxin in some strains of C. botulinum. However, these integrations sites are degraded (except for the C and D types), indicating that the C. botulinum acquired the toxin genes quite far in the evolutionary past. Nevertheless, further transfers still happen via the plasmids and other mobile elements the genes are located on.{{cite journal | vauthors = Poulain B, Popoff MR | title = Why Are Botulinum Neurotoxin-Producing Bacteria So Diverse and Botulinum Neurotoxins So Toxic? | journal = Toxins | volume = 11 | issue = 1 | pages = 34 | date = January 2019 | pmid = 30641949 | pmc = 6357194 | doi = 10.3390/toxins11010034 | doi-access = free }}

Only botulinum toxin types A, B, E, F and H (FA) cause disease in humans. Types A, B, and E are associated with food-borne illness, while type E is specifically associated with fish products. Type C produces limber-neck in birds and type D causes botulism in other mammals.{{cite journal | vauthors = Meurens F, Carlin F, Federighi M, Filippitzi ME, Fournier M, Fravalo P, Ganière JP, Grisot L, Guillier L, Hilaire D, Kooh P, Le Bouquin-Leneveu S, Le Maréchal C, Mazuet C, Morvan H, Petit K, Vaillancourt JP, Woudstra C | title = Clostridium botulinum type C, D, C/D, and D/C: An update | journal = Frontiers in Microbiology | volume = 13 | pages = 1099184 | date = 2023-01-05 | pmid = 36687640 | pmc = 9849819 | doi = 10.3389/fmicb.2022.1099184 | doi-access = free }} No disease is associated with type G.(2013). Chapter 11. Spore-Forming Gram-Positive Bacilli: Bacillus and Clostridium Species. In Brooks G.F., Carroll K.C., Butel J.S., Morse S.A., Mietzner T.A. (Eds), Jawetz, Melnick, & Adelberg's Medical Microbiology, 26th ed. {{ISBN|978-0-07-179031-4}} The "gold standard" for determining toxin type is a mouse bioassay, but the genes for types A, B, E, and F can now be readily differentiated using quantitative PCR.{{cite journal | vauthors = Satterfield BA, Stewart AF, Lew CS, Pickett DO, Cohen MN, Moore EA, Luedtke PF, O'Neill KL, Robison RA | title = A quadruplex real-time PCR assay for rapid detection and differentiation of the Clostridium botulinum toxin genes A, B, E and F | journal = Journal of Medical Microbiology | volume = 59 | issue = Pt 1 | pages = 55–64 | date = January 2010 | pmid = 19779029 | doi = 10.1099/jmm.0.012567-0 | doi-access = free }} Type "H" is in fact a recombinant toxin from types A and F. It can be neutralized by type A antitoxin and no longer is considered a distinct type.{{cite journal | vauthors = Maslanka SE, Lúquez C, Dykes JK, Tepp WH, Pier CL, Pellett S, Raphael BH, Kalb SR, Barr JR, Rao A, Johnson EA | 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 | journal = The Journal of Infectious Diseases | volume = 213 | issue = 3 | pages = 379–385 | date = February 2016 | pmid = 26068781 | pmc = 4704661 | doi = 10.1093/infdis/jiv327 }}

A few strains from organisms genetically identified as other Clostridium species have caused human botulism: C. butyricum has produced type E toxin{{cite journal | vauthors = Aureli P, Fenicia L, Pasolini B, Gianfranceschi M, McCroskey LM, Hatheway CL | title = Two cases of type E infant botulism caused by neurotoxigenic Clostridium butyricum in Italy | journal = The Journal of Infectious Diseases | volume = 154 | issue = 2 | pages = 207–211 | date = August 1986 | pmid = 3722863 | doi = 10.1093/infdis/154.2.207 }} and C. baratii had produced type F toxin.{{cite journal | vauthors = Hall JD, McCroskey LM, Pincomb BJ, Hatheway CL | title = Isolation of an organism resembling Clostridium barati which produces type F botulinal toxin from an infant with botulism | journal = Journal of Clinical Microbiology | volume = 21 | issue = 4 | pages = 654–655 | date = April 1985 | pmid = 3988908 | pmc = 271744 | doi = 10.1128/JCM.21.4.654-655.1985 }} The ability of C. botulinum to naturally transfer neurotoxin genes to other clostridia is concerning, especially in the food industry, where preservation systems are designed to destroy or inhibit only C. botulinum but not other Clostridium species.

Many C. botulinum genes play a role in the breakdown of essential carbohydrates and the metabolism of sugars. Chitin is the preferred source of carbon and nitrogen for C. botulinum.{{cite journal | vauthors = Sebaihia M, Peck MW, Minton NP, Thomson NR, Holden MT, Mitchell WJ, Carter AT, Bentley SD, Mason DR, Crossman L, Paul CJ, Ivens A, Wells-Bennik MH, Davis IJ, Cerdeño-Tárraga AM, Churcher C, Quail MA, Chillingworth T, Feltwell T, Fraser A, Goodhead I, Hance Z, Jagels K, Larke N, Maddison M, Moule S, Mungall K, Norbertczak H, Rabbinowitsch E, Sanders M, Simmonds M, White B, Whithead S, Parkhill J | title = Genome sequence of a proteolytic (Group I) Clostridium botulinum strain Hall A and comparative analysis of the clostridial genomes | journal = Genome Research | volume = 17 | issue = 7 | pages = 1082–1092 | date = July 2007 | pmid = 17519437 | pmc = 1899119 | doi = 10.1101/gr.6282807 }} Hall A strain of C. botulinum has an active chitinolytic system to aid in the breakdown of chitin. Type A and B of C. botulinum production of BoNT is affected by nitrogen and carbon nutrition.{{cite journal | vauthors = Leyer GJ, Johnson EA | title = Repression of toxin production by tryptophan in Clostridium botulinum type E | journal = Archives of Microbiology | volume = 154 | issue = 5 | pages = 443–447 | date = October 1990 | pmid = 2256780 | doi = 10.1007/BF00245225 | bibcode = 1990ArMic.154..443L }}{{cite journal | vauthors = Patterson-Curtis SI, Johnson EA | title = Regulation of neurotoxin and protease formation in Clostridium botulinum Okra B and Hall A by arginine | journal = Applied and Environmental Microbiology | volume = 55 | issue = 6 | pages = 1544–1548 | date = June 1989 | pmid = 2669631 | pmc = 202901 | doi = 10.1128/aem.55.6.1544-1548.1989 | bibcode = 1989ApEnM..55.1544P }}{{Cite journal | vauthors = Schantz EJ, Johnson EA |date=1992 |title=Properties and use of botulinum toxin and other microbial neurotoxins in medicine. |url=https://mmbr.asm.org/content/56/1/80 |journal=Microbiological Reviews |language=en |volume=56 |issue=1 |pages=80–99 |doi=10.1128/MMBR.56.1.80-99.1992 |pmid=1579114 |pmc=372855 |issn=0146-0749}} There is evidence that these processes are also under catabolite repression.{{cite journal | vauthors = Johnson EA, Bradshaw M | title = Clostridium botulinum and its neurotoxins: a metabolic and cellular perspective | journal = Toxicon | volume = 39 | issue = 11 | pages = 1703–1722 | date = November 2001 | pmid = 11595633 | doi = 10.1016/S0041-0101(01)00157-X | bibcode = 2001Txcn...39.1703J }}

Physiological differences and genome sequencing at 16S rRNA level support the subdivision of the C. botulinum species into groups I-IV.{{cite book | title=Clostridium | chapter=Clostridium | Occurrence of Clostridium botulinum | date=January 1, 2003 | doi=10.1016/B0-12-227055-X/00255-8 | chapter-url=https://www.sciencedirect.com/science/article/pii/B012227055X002558 | access-date=February 19, 2021 | pages=1407–1413| publisher=Academic Press | isbn=978-0-12-227055-0 | vauthors = Austin JW }} Some authors have briefly used groups V and VI, corresponding to toxin-producing C. baratii and C. butyricum. What used to be group IV is now C. argentinense.

Although group II cannot degrade native protein such as casein, coagulated egg white, and cooked meat particles, it is able to degrade gelatin.

Human botulism is predominantly caused by group I or II C. botulinum.{{cite journal | vauthors = Carter AT, Peck MW | title = Genomes, neurotoxins and biology of Clostridium botulinum Group I and Group II | journal = Research in Microbiology | volume = 166 | issue = 4 | pages = 303–317 | date = May 2015 | pmid = 25445012 | pmc = 4430135 | doi = 10.1016/j.resmic.2014.10.010 | doi-access = free }} Group III organisms mainly cause diseases in non-human animals.

In the laboratory, C. botulinum is usually isolated in tryptose sulfite cycloserine (TSC) growth medium in an anaerobic environment with less than 2% oxygen. This can be achieved by several commercial kits that use a chemical reaction to replace O₂ with CO₂. C. botulinum (groups I through III) is a lipase-positive microorganism that grows between pH of 4.8 and 7.0 and cannot use lactose as a primary carbon source, characteristics important for biochemical identification.{{cite book|title=Brock Biology of Microorganisms|edition=11th| veditors = Madigan MT, Martinko JM |publisher=Prentice Hall|year=2005|isbn=978-0-13-144329-7}}

The exact mechanism behind sporulation of C. botulinum is not known. Different strains of C. botulinum can be divided into three different groups, group I, II, and III, based on environmental conditions like heat resistance, temperature, and biome.{{cite journal | vauthors = Portinha IM, Douillard FP, Korkeala H, Lindström M | title = Sporulation Strategies and Potential Role of the Exosporium in Survival and Persistence of Clostridium botulinum | journal = International Journal of Molecular Sciences | volume = 23 | issue = 2 | page = 754 | date = January 2022 | pmid = 35054941 | pmc = 8775613 | doi = 10.3390/ijms23020754 | doi-access = free }}> Within each group, different strains will use different strategies to adapt to their environment to survive. Unlike other clostridial species, C. botulinum spores will sporulate as it enters the stationary phase.{{cite journal | vauthors = Shen A, Edwards AN, Sarker MR, Paredes-Sabja D | title = Sporulation and Germination in Clostridial Pathogens | journal = Microbiology Spectrum | volume = 7 | issue = 6 | date = November 2019 | pmid = 31858953 | pmc = 6927485 | doi = 10.1128/microbiolspec.GPP3-0017-2018 | veditors = Fischetti VA, Novick RP, Ferretti JJ, Portnoy DA, Braunstein M, Rood JI }} C. botulinum relies on quorum-sensing to initiate the sporulation process. C. botulinum spores are not found in human feces unless the individual has contracted botulism,{{Cite journal |url=https://jamanetwork.com/journals/jama/fullarticle/356218 |title= Coproexamination for Botulinal Toxin and Clostridium botulinum |access-date=2024-04-11 |journal=JAMA |date= 1977 |doi=10.1001/jama.1977.03280180033021 | vauthors = Dowell VR |volume= 238 |issue= 17 |page= 1829 |url-access= subscription }} but C. botulinum cannot spread from person to person.{{Cite web |title=Botulism |url=https://www.who.int/news-room/fact-sheets/detail/botulism |access-date=2024-04-16 |website=www.who.int |language=en}}

The most common motility structure for C. botulinum is a flagellum. Though this structure is not found in all strains of C. botulinum, most produce peritrichous flagella.{{Cite journal |last1=Paul |first1=Catherine J. |last2=Twine |first2=Susan M. |last3=Tam |first3=Kevin J. |last4=Mullen |first4=James A. |last5=Kelly |first5=John F. |last6=Austin |first6=John W. |last7=Logan |first7=Susan M. |date=May 2007 |title=Flagellin Diversity in Clostridium botulinum Groups I and II: a New Strategy for Strain Identification |journal=Applied and Environmental Microbiology |language=en |volume=73 |issue=9 |pages=2963–2975 |doi=10.1128/AEM.02623-06 |issn=0099-2240 |pmc=1892883 |pmid=17351097|bibcode=2007ApEnM..73.2963P }} When comparing the different strains, there is also differences in the length of the flagella and how many are present on the cell.

{{See also|Botulism#Prevention}}

C. botulinum is a soil bacterium. The spores can survive in most environments and are very hard to kill. They can survive the temperature of boiling water at sea level, thus many foods are canned with a pressurized boil that achieves even higher temperatures, sufficient to kill the spores.{{Cite web |date=2019-06-06 |title=Prevent Botulism |url=https://www.cdc.gov/botulism/consumer.html |access-date=2023-04-23 |website=Centers for Disease Control and Prevention (CDC) |language=en-us}}{{Cite web |title=Botulism: take care when canning low-acid foods |url=https://extension.umn.edu/sanitation-and-illness/botulism |access-date=2023-04-23 |website=extension.umn.edu |language=en}} This bacteria is widely distributed in nature and can be assumed to be present on all food surfaces. Its optimum growth temperature is within the mesophilic range. In spore form, it is a heat resistant pathogen that can survive in low acid foods and grow to produce toxins. The toxin attacks the nervous system and will kill an adult at a dose of around 75 ng.{{cite book |title=Biological Safety: principles and practices |vauthors=Fleming DO |publisher=ASM Press |volume=2000 |page=267}} Botulinum toxin can be destroyed by holding food at 100 °C for 10 minutes; however, because of its potency, this is not recommended by the USA's FDA as a means of control.{{cite web |title=Chapter 13: Clostridium botulinum Toxin Formation |url=https://www.fda.gov/files/food/published/Fish-and-Fishery-Products-Hazards-and-Controls-Guidance-Chapter-13-Download.pdf |url-status=live |archive-url=https://web.archive.org/web/20210208183813/https://www.fda.gov/files/food/published/Fish-and-Fishery-Products-Hazards-and-Controls-Guidance-Chapter-13-Download.pdf |archive-date=2021-02-08 |access-date=18 March 2022 |website=Fda.gov}}

Botulism poisoning can occur due to preserved or home-canned, low-acid food that was not processed using correct preservation times and/or pressure.{{cite web |title=Home Canning and Botulism |url=https://www.cdc.gov/foodsafety/communication/home-canning-and-botulism.html#:~:text=Pressure%20canning%20is%20the%20only,meats%2C%20fish%2C%20and%20seafood |access-date=14 April 2021 |website=Centers for Disease Control and Prevention}} Growth of the bacterium can be prevented by high acidity, high ratio of dissolved sugar, high levels of oxygen, very low levels of moisture, or storage at temperatures below 3 °C (38 °F) for type A. For example, in a low-acid, canned vegetable such as green beans that are not heated enough to kill the spores (i.e., a pressurized environment) may provide an oxygen-free medium for the spores to grow and produce the toxin. However, pickles are sufficiently acidic to prevent growth;{{cite journal | vauthors = Ito KA, Chen JK, Lerke PA, Seeger ML, Unverferth JA | title = Effect of acid and salt concentration in fresh-pack pickles on the growth of Clostridium botulinum spores | journal = Applied and Environmental Microbiology | volume = 32 | issue = 1 | pages = 121–124 | date = July 1976 | pmid = 9898 | pmc = 170016 | doi = 10.1128/aem.32.1.121-124.1976 | bibcode = 1976ApEnM..32..121I }} even if the spores are present, they pose no danger to the consumer.

Honey, corn syrup, and other sweeteners may contain spores, but the spores cannot grow in a highly concentrated sugar solution; however, when a sweetener is diluted in the low-oxygen, low-acid digestive system of an infant, the spores can grow and produce toxin. As soon as infants begin eating solid food, the digestive juices become too acidic for the bacterium to grow.{{cite web |title=Botulism |url=https://www.lecturio.com/concepts/botulism/ |access-date=5 July 2021 |website=The Lecturio Medical Concept Library}}

The control of food-borne botulism caused by C. botulinum is based almost entirely on thermal destruction (heating) of the spores or inhibiting spore germination into bacteria and allowing cells to grow and produce toxins in foods. Conditions conducive of growth are dependent on various environmental factors.

Growth of C. botulinum is a risk in low acid foods as defined by having a pH above 4.6{{cite web |title=Guidance for Commercial Processors of Acidified & Low-Acid Canned Foods |url=https://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/AcidifiedLACF/default.htm |archive-url=https://web.archive.org/web/20130324105106/http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/AcidifiedLACF/default.htm |url-status=dead |archive-date=March 24, 2013 |access-date=8 October 2016 |publisher=U.S. Food and Drug Administration}} although growth is significantly retarded for pH below 4.9.{{cite journal | vauthors = Odlaug TE, Pflug IJ | title = Clostridium botulinum growth and toxin production in tomato juice containing Aspergillus gracilis | journal = Applied and Environmental Microbiology | volume = 37 | issue = 3 | pages = 496–504 | date = March 1979 | pmid = 36843 | pmc = 243244 | doi = 10.1128/aem.37.3.496-504.1979 | bibcode = 1979ApEnM..37..496O }}

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C. botulinum was first recognized and isolated in 1895 by Emile van Ermengem from home-cured ham implicated in a botulism outbreak.{{cite journal | vauthors = van Ergmengem E | year = 1897 | title = Über einen neuen anaeroben Bacillus und seine Beziehungen Zum Botulismus | journal = Zeitschrift für Hygiene und Infektionskrankheiten | volume = 26 | pages = 1–8}} The isolate was originally named Bacillus botulinus, after the Latin word for sausage, botulus. ("Sausage poisoning" was a common problem in 18th- and 19th-century Germany, and was most likely caused by botulism.){{cite journal | vauthors = Erbguth FJ | title = Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin | journal = Movement Disorders | volume = 19 | issue = Suppl 8 | pages = S2–S6 | date = March 2004 | pmid = 15027048 | doi = 10.1002/mds.20003 | s2cid = 8190807 }} However, isolates from subsequent outbreaks were always found to be anaerobic spore formers, so Ida A. Bengtson proposed that both be placed into the genus Clostridium, as the genus Bacillus was restricted to aerobic spore-forming rods.{{cite journal | vauthors = Bengston IA | year = 1924 | title = Studies on organisms concerned as causative factors in botulism | journal = Bulletin (Hygienic Laboratory (U.S.)) | volume = 136 | page = 101 fv|url=https://babel.hathitrust.org/cgi/pt?id=mdp.39015007772703}}

Since 1959, all species producing the botulinum neurotoxins (types A–G) have been designated C. botulinum. Substantial phenotypic and genotypic evidence exists to demonstrate heterogeneity within the species, with at least four clearly-defined "groups" (see {{section link||Groups}}) straddling other species, implying that they each deserve to be a genospecies.{{cite book|chapter=Taxonomic Relationships among the Clostridia | vauthors = Uzal FA, Songer JG, Prescott JF, Popoff MR |title=Clostridial Diseases of Animals |date=21 June 2016 | pages = 1–5 |doi=10.1002/9781118728291.ch1|isbn=978-1-118-72829-1}}{{cite journal | vauthors = Smith T, Williamson CH, Hill K, Sahl J, Keim P | title = Botulinum Neurotoxin-Producing Bacteria. Isn't It Time that We Called a Species a Species? | journal = mBio | volume = 9 | issue = 5 | date = September 2018 | pmid = 30254123 | pmc = 6156192 | doi = 10.1128/mbio.01469-18 }}

The situation as of 2018 is as follows:

• C. botulinum type G (= group IV) strains are since 1988 their own species, C. argentinense.{{cite journal | vauthors = Suen JC, Hatheway CL, Steigerwalt AG, Brenner DJ | year = 1988 | title = Clostridium argentinense sp.nov.: a genetically homogeneous group composed of all strains of Clostridium botulinum type G and some nonttoxigenic strains previously identified as Clostridium subterminale or Clostridium hastiforme | journal = International Journal of Systematic Bacteriology | volume = 38 | pages = 375–381 | doi = 10.1099/00207713-38-4-375 | doi-access = free}}
• Group I C. botulinum strains that do not produce a botulin toxin are referred to as C. sporogenes. Both names are conserved names since 1999.{{cite journal | vauthors = | title = Rejection of Clostridium putrificum and conservation of Clostridium botulinum and Clostridium sporogenes-Opinion 69. Judicial Commission of the International Committee on Systematic Bacteriology | journal = International Journal of Systematic Bacteriology | volume = 49 Pt 1 | issue = 1 | pages = 339 | date = January 1999 | pmid = 10028279 | doi = 10.1099/00207713-49-1-339 | doi-access = free }} Group I also contains C. combesii.{{cite web |title=Species: Clostridium combesii |url=https://lpsn.dsmz.de/species/clostridium-combesii |website=lpsn.dsmz.de |language=en}}
• All other botulinum toxin-producing bacteria, not otherwise classified as C. baratii or C. butyricum,{{cite journal | vauthors = Arahal DR, Busse HJ, Bull CT, Christensen H, Chuvochina M, Dedysh SN, Fournier PE, Konstantinidis KT, Parker CT, Rossello-Mora R, Ventosa A, Göker M | title = Judicial Opinions 112-122 | journal = International Journal of Systematic and Evolutionary Microbiology | volume = 72 | issue = 8 | date = August 2022 | pmid = 35947640 | doi = 10.1099/ijsem.0.005481 | s2cid = 251470203 |quote=Opinion 121 denies the request to revise Opinion 69 and notes that Opinion 69 does not have the undesirable consequences emphasized in the request [Dobritsa et al. 2018].}} is called C. botulinum. This group still contains three genogroups.

Smith et al. (2018) argues that group I should be called C. parabotulinum and group III be called C. novyi sensu lato, leaving only group II in C. botulinum. This argument is not accepted by the LPSN and would cause an unjustified change of the type strain under the Prokaryotic Code. (The current type strain ATCC 25763 falls into group I.) Dobritsa et al. (2018) argues, without formal descriptions, that group II can potentially be made into two new species.{{cite journal | vauthors = Dobritsa AP, Kutumbaka KK, Samadpour M | title = Reclassification of Eubacterium combesii and discrepancies in the nomenclature of botulinum neurotoxin-producing clostridia: Challenging Opinion 69. Request for an Opinion | journal = International Journal of Systematic and Evolutionary Microbiology | volume = 68 | issue = 9 | pages = 3068–3075 | date = September 2018 | pmid = 30058996 | doi = 10.1099/ijsem.0.002942 | doi-access = free }}

The complete genome of C. botulinum ATCC 3502 has been sequenced at Wellcome Trust Sanger Institute in 2007. This strain encodes a type "A" toxin.{{cite web |title=Clostridium botulinum A str. ATCC 3502 genome assembly ASM6358v1 |url=https://www.ncbi.nlm.nih.gov/datasets/genome/GCF_000063585.1/ |website=NCBI |language=en}}

Physicians may consider the diagnosis of botulism based on a patient's clinical presentation, which classically includes an acute onset of bilateral cranial neuropathies and symmetric descending weakness.{{cite journal | vauthors = Cherington M | title = Clinical spectrum of botulism | journal = Muscle & Nerve | volume = 21 | issue = 6 | pages = 701–710 | date = June 1998 | pmid = 9585323 | doi = 10.1002/(sici)1097-4598(199806)21:6<701::aid-mus1>3.0.co;2-b }}{{cite journal | vauthors = Cai S, Singh BR, Sharma S | title = Botulism diagnostics: from clinical symptoms to in vitro assays | journal = Critical Reviews in Microbiology | volume = 33 | issue = 2 | pages = 109–125 | date = April 2007 | pmid = 17558660 | doi = 10.1080/10408410701364562 | s2cid = 23470999 }} Other key features of botulism include an absence of fever, symmetric neurologic deficits, normal or slow heart rate and normal blood pressure, and no sensory deficits except for blurred vision.{{Cite web |title=Diagnosis and Treatment {{!}} Botulism |url=https://www.cdc.gov/botulism/testing-treatment.html |access-date=2017-10-08 |publisher=CDC |language=en-us}}{{Cite news |title=Botulism: Rare but serious food poisoning |url=https://www.mayoclinic.org/diseases-conditions/botulism/basics/symptoms/con-20025875 |access-date=2017-11-18 |publisher=Mayo Clinic |language=en}} A careful history and physical examination is paramount to diagnose the type of botulism, as well as to rule out other conditions with similar findings, such as Guillain–Barré syndrome, stroke, and myasthenia gravis.{{cite journal | vauthors = Rao AK, Sobel J, Chatham-Stephens K, Luquez C | title = Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021 | language = en-us | journal = MMWR. Recommendations and Reports | volume = 70 | issue = 2 | pages = 1–30 | date = May 2021 | pmid = 33956777 | pmc = 8112830 | doi = 10.15585/mmwr.rr7002a1 }} Depending on the type of botulism considered, different tests for diagnosis may be indicated.

• Foodborne botulism: serum analysis for toxins by bioassay in mice should be done, as the demonstration of the toxins is diagnostic.{{cite journal | vauthors = Lindström M, Korkeala H | title = Laboratory diagnostics of botulism | journal = Clinical Microbiology Reviews | volume = 19 | issue = 2 | pages = 298–314 | date = April 2006 | pmid = 16614251 | pmc = 1471988 | doi = 10.1128/CMR.19.2.298-314.2006 }}
• Wound botulism: isolation of C. botulinum from the wound site should be attempted, as growth of the bacteria is diagnostic.{{cite journal | vauthors = Akbulut D, Grant KA, McLauchlin J | title = Improvement in laboratory diagnosis of wound botulism and tetanus among injecting illicit-drug users by use of real-time PCR assays for neurotoxin gene fragments | journal = Journal of Clinical Microbiology | volume = 43 | issue = 9 | pages = 4342–4348 | date = September 2005 | pmid = 16145075 | pmc = 1234055 | doi = 10.1128/JCM.43.9.4342-4348.2005 }}
• Adult enteric and infant botulism: isolation and growth of C. botulinum from stool samples is diagnostic.{{cite journal | vauthors = Dezfulian M, McCroskey LM, Hatheway CL, Dowell VR | title = Selective medium for isolation of Clostridium botulinum from human feces | journal = Journal of Clinical Microbiology | volume = 13 | issue = 3 | pages = 526–531 | date = March 1981 | pmid = 7016901 | pmc = 273826 | doi = 10.1128/JCM.13.3.526-531.1981 }} Infant botulism is a diagnosis which is often missed in the emergency room.{{cite journal | vauthors = Antonucci L, Locci C, Schettini L, Clemente MG, Antonucci R | title = Infant botulism: an underestimated threat | journal = Infectious Diseases | volume = 53 | issue = 9 | pages = 647–660 | date = September 2021 | pmid = 33966588 | doi = 10.1080/23744235.2021.1919753 }}

Other tests that may be helpful in ruling out other conditions are:

• Electromyography (EMG) or antibody studies may help with the exclusion of myasthenia gravis and Lambert–Eaton myasthenic syndrome (LEMS).{{cite journal | vauthors = O'Suilleabhain P, Low PA, Lennon VA | title = Autonomic dysfunction in the Lambert-Eaton myasthenic syndrome: serologic and clinical correlates | journal = Neurology | volume = 50 | issue = 1 | pages = 88–93 | date = January 1998 | pmid = 9443463 | doi = 10.1212/wnl.50.1.88 | s2cid = 39437882 }}
• Collection of cerebrospinal fluid (CSF) protein and blood assist with the exclusion of Guillan-Barre syndrome and stroke.{{cite journal | vauthors = Mechem CC, Walter FG | title = Wound botulism | journal = Veterinary and Human Toxicology | volume = 36 | issue = 3 | pages = 233–237 | date = June 1994 | pmid = 8066973 | url = https://pubmed.ncbi.nlm.nih.gov/8066973/ }}
• Detailed physical examination of the patient for any rash or tick presence helps with the exclusion of any tick transmitted tick paralysis.{{cite journal | vauthors = Taraschenko OD, Powers KM | title = Neurotoxin-induced paralysis: a case of tick paralysis in a 2-year-old child | journal = Pediatric Neurology | volume = 50 | issue = 6 | pages = 605–607 | date = June 2014 | pmid = 24679414 | doi = 10.1016/j.pediatrneurol.2014.01.041 }}

Signs and symptoms of foodborne botulism typically begin between 18 and 36 hours after the toxin gets into your body, but can range from a few hours to several days, depending on the amount of toxin ingested. Symptoms include:{{cite journal | vauthors = Lonati D, Schicchi A, Crevani M, Buscaglia E, Scaravaggi G, Maida F, Cirronis M, Petrolini VM, Locatelli CA | title = Foodborne Botulism: Clinical Diagnosis and Medical Treatment | journal = Toxins | volume = 12 | issue = 8 | pages = 509 | date = August 2020 | pmid = 32784744 | pmc = 7472133 | doi = 10.3390/toxins12080509 | doi-access = free }}{{cite web |date=June 13, 2015 |title=Botulism Symptoms |url=http://www.mayoclinic.org/diseases-conditions/botulism/basics/symptoms/con-20025875 |access-date=January 25, 2016 |publisher=Mayo Clinic}}

• Double vision
• Blurred vision
• Ptosis
• Nausea, vomiting, and abdominal cramps
• Slurred speech
• Trouble breathing
• Difficulty in swallowing
• Dry mouth
• Muscle weakness
• Constipation
• Reduced or absent deep tendon reactions, such as in the knee

Most people who develop wound botulism inject drugs several times a day, so determining a timeline of when onset symptoms first occurred and when the toxin entered the body can be difficult. It is more common in people who inject black tar heroin.{{Cite web |date=2022-05-31 |title=Injection Drug Use and Wound Botulism {{!}} Botulism {{!}} CDC |url=https://www.cdc.gov/botulism/wound-botulism.html |access-date=2024-04-17 |website=www.cdc.gov |language=en-us}} Wound botulism signs and symptoms include:{{cite journal | vauthors = Schulte M, Hamsen U, Schildhauer TA, Ramczykowski T | title = Effective and rapid treatment of wound botulism, a case report | journal = BMC Surgery | volume = 17 | issue = 1 | pages = 103 | date = October 2017 | pmid = 29073888 | pmc = 5658925 | doi = 10.1186/s12893-017-0300-4 | doi-access = free }}

• Difficulty swallowing or speaking
• Facial weakness on both sides of the face
• Blurred or double vision
• Ptosis
• Trouble breathing
• Paralysis

If infant botulism is related to food, such as honey, problems generally begin within 18 to 36 hours after the toxin enters the baby's body. Signs and symptoms include:

• Constipation (often the first sign)
• Floppy movements due to muscle weakness and trouble controlling the head
• Weak cry
• Irritability
• Drooling
• Ptosis
• Tiredness
• Difficulty sucking or feeding
• Paralysis

Purified botulinum toxin is diluted by a physician for treatment of:{{Cite journal | vauthors = Chiu SY, Patel B, Burns MR, Legacy J, Shukla AW, Ramirez-Zamora A, Deeb W, Malaty IA |date=2020-02-27 |title=High-dose Botulinum Toxin Therapy: Safety, Benefit, and Endurance of Efficacy |journal=Tremor and Other Hyperkinetic Movements |volume=10 |doi=10.5334/tohm.527 |doi-access=free |pmid=32149014 |pmc=7052428 |issn=2160-8288}}

• Congenital pelvic tilt
• Spasmodic dysphasia (the inability of the muscles of the larynx)
• Achalasia (esophageal stricture)
• Strabismus (crossed eyes)
• Paralysis of the facial muscles
• Failure of the cervix
• Blinking frequently
• Anti-cancer drug delivery{{cite journal | vauthors = Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Hauer J, Layton M, Lillibridge S, Osterholm MT, O'Toole T, Parker G, Perl TM, Russell PK, Swerdlow DL, Tonat K | title = Botulinum toxin as a biological weapon: medical and public health management | journal = JAMA | volume = 285 | issue = 8 | pages = 1059–1070 | date = February 2001 | pmid = 11209178 | doi = 10.1001/jama.285.8.1059 }}

A very rare form of botulism that occurs by the same route as infant botulism but is among adults. Occurs rarely and sporadically. Signs and symptoms include:{{cite journal | vauthors = Harris RA, Anniballi F, Austin JW | title = Adult Intestinal Toxemia Botulism | journal = Toxins | volume = 12 | issue = 2 | pages = 81 | date = January 2020 | pmid = 31991691 | pmc = 7076759 | doi = 10.3390/toxins12020081 | doi-access = free }}

• Abdominal pain
• Blurred vision
• Diarrhea
• Dysarthria
• Imbalance
• Weakness in arms and hand area{{cite web | title = Botulism | url = https://www.cdc.gov/botulism/index.html | work = Centers for Disease Control and Prevention | access-date = 23 October 2016 }}

In the case of a diagnosis or suspicion of botulism, patients should be hospitalized immediately, even if the diagnosis and/or tests are pending. Additionally if botulism is suspected, patients should be treated immediately with antitoxin therapy in order to reduce mortality. Immediate intubation is also highly recommended, as respiratory failure is the primary cause of death from botulism.{{cite journal | vauthors = Witoonpanich R, Vichayanrat E, Tantisiriwit K, Wongtanate M, Sucharitchan N, Oranrigsupak P, Chuesuwan A, Nakarawat W, Tima A, Suwatcharangkoon S, Ingsathit A, Rattanasiri S, Wananukul W | title = Survival analysis for respiratory failure in patients with food-borne botulism | journal = Clinical Toxicology | volume = 48 | issue = 3 | pages = 177–183 | date = March 2010 | pmid = 20184431 | doi = 10.3109/15563651003596113 | s2cid = 23108891 }}{{cite journal | vauthors = Sandrock CE, Murin S | title = Clinical predictors of respiratory failure and long-term outcome in black tar heroin-associated wound botulism | journal = Chest | volume = 120 | issue = 2 | pages = 562–566 | date = August 2001 | pmid = 11502659 | doi = 10.1378/chest.120.2.562 }}{{cite journal | vauthors = Wongtanate M, Sucharitchan N, Tantisiriwit K, Oranrigsupak P, Chuesuwan A, Toykeaw S, Suputtamongkol Y | title = Signs and symptoms predictive of respiratory failure in patients with foodborne botulism in Thailand | journal = The American Journal of Tropical Medicine and Hygiene | volume = 77 | issue = 2 | pages = 386–389 | date = August 2007 | pmid = 17690419 | doi = 10.4269/ajtmh.2007.77.386 | doi-access = free }}

In North America, an equine-derived heptavalent botulinum antitoxin is used to treat all serotypes of non-infant naturally occurring botulism. For infants less than one year of age, botulism immune globulin is used to treat type A or type B.{{Cite web | work = Health Canada |date=2012-07-18 |title=Botulism - Guide for Healthcare Professionals |url=https://www.canada.ca/en/health-canada/services/food-nutrition/legislation-guidelines/guidance-documents/botulism-guide-healthcare-professionals-2012.html |access-date=2023-11-01 }}{{Cite web |title=Investigational Heptavalent Botulinum Antitoxin (HBAT) to Replace Licensed Botulinum Antitoxin AB and Investigational Botulinum Antitoxin E |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5910a4.htm |access-date=2023-11-01 |website=www.cdc.gov}}

Outcomes vary between one and three months, but with prompt interventions, mortality from botulism ranges from less than 5 percent to 8 percent.{{cite journal | vauthors = Varma JK, Katsitadze G, Moiscrafishvili M, Zardiashvili T, Chokheli M, Tarkhashvili N, Jhorjholiani E, Chubinidze M, Kukhalashvili T, Khmaladze I, Chakvetadze N, Imnadze P, Hoekstra M, Sobel J | title = Signs and symptoms predictive of death in patients with foodborne botulism--Republic of Georgia, 1980-2002 | journal = Clinical Infectious Diseases | volume = 39 | issue = 3 | pages = 357–362 | date = August 2004 | pmid = 15307002 | doi = 10.1086/422318 | s2cid = 20675701 | doi-access = }}

There used to be a formalin-treated toxoid vaccine against botulism (serotypes A-E), but it was discontinued in 2011 due to declining potency in the toxoid stock. It was originally intended for people at risk of exposure. A few new vaccines are under development.{{cite journal | vauthors = Sundeen G, Barbieri JT | title = Vaccines against Botulism | journal = Toxins | volume = 9 | issue = 9 | page = 268 | date = September 2017 | pmid = 28869493 | pmc = 5618201 | doi = 10.3390/toxins9090268 | doi-access = free }}

C. botulinum is used to prepare the medicaments Botox, Dysport, Xeomin, and Neurobloc used to selectively paralyze muscles to temporarily relieve muscle function. It has other "off-label" medical purposes, such as treating severe facial pain, such as that caused by trigeminal neuralgia.{{cite journal | vauthors = Guardiani E, Sadoughi B, Blitzer A, Sirois D | title = A new treatment paradigm for trigeminal neuralgia using Botulinum toxin type A | journal = The Laryngoscope | volume = 124 | issue = 2 | pages = 413–417 | date = February 2014 | pmid = 23818108 | doi = 10.1002/lary.24286 }}

Botulinum toxin produced by C. botulinum is often believed to be a potential bioweapon as it is so potent that it takes about 75 nanograms to kill a person ({{LD50}} of 1 ng/kg, assuming an average person weighs ~75 kg); 1 kilogram of it would be enough to kill the entire human population.

A "mouse protection" or "mouse bioassay" test determines the type of C. botulinum toxin present using monoclonal antibodies. An enzyme-linked immunosorbent assay (ELISA) with digoxigenin-labeled antibodies can also be used to detect the toxin,{{cite journal | vauthors = Sharma SK, Ferreira JL, Eblen BS, Whiting RC | title = Detection of type A, B, E, and F Clostridium botulinum neurotoxins in foods by using an amplified enzyme-linked immunosorbent assay with digoxigenin-labeled antibodies | journal = Applied and Environmental Microbiology | volume = 72 | issue = 2 | pages = 1231–1238 | date = February 2006 | pmid = 16461671 | pmc = 1392902 | doi = 10.1128/AEM.72.2.1231-1238.2006 | bibcode = 2006ApEnM..72.1231S | doi-access = free }} and quantitative PCR can detect the toxin genes in the organism.

A number of quantitative surveys for C. botulinum spores in the environment have suggested a prevalence of specific toxin types in given geographic areas, which remain unexplained.

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• {{cite journal | vauthors = Sobel J | title = Botulism | journal = Clinical Infectious Diseases | volume = 41 | issue = 8 | pages = 1167–1173 | date = October 2005 | pmid = 16163636 | doi = 10.1086/444507 | doi-access = free }}

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{{Toxins}}

{{Gram-positive firmicutes diseases}}

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Category:Bacteria described in 1896

Category:Botulism

botulinum

Category:Food microbiology

Category:Gram-positive bacteria

Category:Pathogenic bacteria