View source for Clostridium botulinum

{{Short description|Species of endospore forming bacterium}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Speciesbox
| image = Clostridium botulinum_01.png
| image_caption = ''Clostridium botulinum'' stained with [[gentian violet]].
| taxon = Clostridium botulinum
| authority = [[van Ermengem]], 1896
}}

'''''Clostridium botulinum''''' is a [[Gram-positive bacteria|gram-positive]],<ref name="Tiwari_2021">{{cite book | vauthors = Tiwari A, Nagalli S | chapter = Clostridium Botulinum |date=2021| chapter-url= https://www.ncbi.nlm.nih.gov/books/NBK553081/|title =StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=31971722|access-date=2021-09-23}}</ref> [[Bacillus (shape)|rod-shaped]], [[Anaerobic organism|anaerobic]], [[endospore|spore-forming]], [[Motility|motile]] [[bacterium]] that has the ability to produce [[botulinum toxin]], which is a [[neurotoxin]] and the deadliest known substance ever recorded in the chemical literature.<ref name="Montecucco2005">{{cite journal |vauthors=Montecucco C, Molgó J |date=June 2005 |title=Botulinal neurotoxins: revival of an old killer |journal=Current Opinion in Pharmacology |volume=5 |issue=3 |pages=274–279 |doi=10.1016/j.coph.2004.12.006 |pmid=15907915}}</ref><ref>{{cite journal |vauthors=Košenina S, Masuyer G, Zhang S, Dong M, Stenmark P |date=June 2019 |title=Crystal structure of the catalytic domain of the Weissella oryzae botulinum-like toxin |journal=FEBS Letters |volume=593 |issue=12 |pages=1403–1410 |doi=10.1002/1873-3468.13446 |pmid=31111466 |doi-access=free |title-link=doi}}</ref><ref>{{Cite journal |vauthors=Dhaked RK, Singh MK, Singh P, Gupta P |date=November 2010 |title=Botulinum toxin: Bioweapon & magic drug |journal=Indian Journal of Medical Research |volume=132 |issue=5 |pages=489–503 |doi=10.4103/IJMR.2010_132_05_489 |pmc=3028942 |pmid=21149997 |doi-access=free}}</ref><ref>{{Cite journal |last1=Rossetto |first1=Ornella |last2=Pirazzini |first2=Marco |last3=Montecucco |first3=Cesare |date=August 2014 |title=Botulinum neurotoxins: genetic, structural and mechanistic insights |url=https://www.nature.com/articles/nrmicro3295 |journal=Nature Reviews Microbiology |language=en |volume=12 |issue=8 |pages=535–549 |doi=10.1038/nrmicro3295 |pmid=24975322 |issn=1740-1534}}</ref><ref name="pmid19573697">{{cite journal |vauthors=Peck MW |title=Biology and genomic analysis of Clostridium botulinum |journal=Advances in Microbial Physiology |volume=55 |issue= |pages=183–265, 320 |date=2009 |pmid=19573697 |doi=10.1016/S0065-2911(09)05503-9 |isbn=978-0-12-374790-7 |url=}}</ref><ref name="Lindström">{{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 }}</ref>

''C. botulinum'' is a diverse group of [[pathogenic bacteria]]. Initially, they were grouped together by their ability to produce botulinum toxin and are now known as four distinct groups, ''C. botulinum'' groups I–IV. Along with some strains of ''[[Clostridium butyricum]]'' and ''[[Clostridium baratii]]'', these bacteria all produce the toxin.<ref name="pmid19573697"/>

Botulinum toxin can cause [[botulism]], a severe [[Flaccid paralysis|flaccid paralytic]] disease in humans and other animals.<ref name="Lindström" /> The botulinum toxin is the most potent toxin known in scientific literature, natural or synthetic, with a lethal dose of 1.3–2.1&nbsp;ng/kg in humans.<ref>{{cite journal | vauthors = Košenina S, Masuyer G, Zhang S, Dong M, Stenmark P | title = Crystal structure of the catalytic domain of the Weissella oryzae botulinum-like toxin | journal = FEBS Letters | volume = 593 | issue = 12 | pages = 1403–1410 | date = June 2019 | pmid = 31111466 | doi = 10.1002/1873-3468.13446 | doi-access = free }}</ref><ref name="SherrisCh19">(2010). Chapter 19. ''Clostridium'', ''Peptostreptococcus'', ''Bacteroides'', and Other Anaerobes. In Ryan K.J., Ray C (Eds), ''Sherris Medical Microbiology'', 5th ed. {{ISBN|978-0-07-160402-4}}</ref>

''C. botulinum'' is commonly associated with bulging [[canning (food)|canned]] food; misshapen cans can be due to an internal increase in pressure caused by gas produced by bacteria.<ref name="IFAS">{{cite web| vauthors = Schneider KR, Silverberg R, Chang A, Goodrich Schneider RM |title=Preventing Foodborne Illness: ''Clostridium botulinum''|url=http://edis.ifas.ufl.edu/fs104|website=edis.ifas.ufl.edu|publisher=University of Florida IFAS Extension|access-date=7 February 2017|language=en|date=9 January 2015}}</ref>

''C. botulinum'' is responsible for food-borne [[botulism]] (ingestion of preformed toxin), infant botulism (intestinal infection with toxin-forming ''C. botulinum''), and wound botulism (infection of a wound with ''C. botulinum'').  ''C. botulinum'' produces heat-resistant [[endospore]]s that are commonly found in soil and are able to survive under adverse conditions.<ref name="pmid19573697"/>

==Microbiology==

''C. botulinum ''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.<ref name="Brock">{{cite book | vauthors = Doyle MP | title = Food Microbiology: Fundamentals and Frontiers | publisher = ASM Press| year = 2007 | isbn = 978-1-55581-208-9}}</ref> ''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 [[serotype]]s (A–G) based on the [[antigenicity]] of the botulinum toxin produced.<ref>{{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 }}</ref><ref>{{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 }}</ref> On the level visible to DNA sequences, the phenotypic grouping matches the results of whole-genome and [[rRNA]] analyses,<ref name="ScienceDirect 2003 pp. 1407"/><ref name=Dobritsa18/> and setotype grouping approximates the result of analyses focused specifically on the toxin sequence. The two [[phylogenetic tree]]s do not match because of the ability of the toxin [[gene cluster]] to be horizontally transferred.<ref name=Hill>{{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}}</ref>

=== Serotypes ===
{{Main|Botulinum toxin}}
[[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.<ref name="SherrisCh19"/>  Toxins can be further differentiated into subtypes on the bases of smaller variations.<ref>{{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 | bibcode = 2017Toxin...9...38P | doi-access = free }}</ref>
However, all types of botulinum toxin are rapidly destroyed by heating to 100&nbsp;°C for 15 minutes (900 seconds). 80&nbsp;°C for 30 minutes also destroys BoNT.<ref>{{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}}</ref><ref>{{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 }}</ref>

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]].<ref>{{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 }}</ref> 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.<ref name="Hill" />

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.<ref>{{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 | page = 34 | date = January 2019 | pmid = 30641949 | pmc = 6357194 | doi = 10.3390/toxins11010034 | doi-access = free }}</ref>

==== Toxin types in disease ====
[[Botulinum toxin]] types A, B, E, F and H (FA) cause disease in humans.  Types A, B, and E <!--or F?--> are associated with food-borne illness, while type E <!--or F?--> is specifically associated with fish products. Type C produces limber-neck in birds and type D causes botulism in other mammals.<ref>{{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 | article-number = 1099184 | date = 2023-01-05 | pmid = 36687640 | pmc = 9849819 | doi = 10.3389/fmicb.2022.1099184 | doi-access = free }}</ref>  No disease is associated with type G.<ref>(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}}</ref>  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]].<ref name="Satterfield, B. A. 2010">{{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 }}</ref> 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.<ref name="pmid26068781">{{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 }}</ref>

A few strains from organisms genetically identified as other ''Clostridium'' species have caused human botulism: ''C. butyricum'' has produced type E toxin<ref>{{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 }}</ref> and ''C. baratii'' has produced type F toxin.<ref>{{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 }}</ref> 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.<ref name="Hill" />

=== Metabolism ===
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''.<ref name=":3">{{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 }}</ref> Hall A strain of ''C. botulinum'' has an active chitinolytic system to aid in the breakdown of chitin.<ref name=":3" /> Type A and B of ''C. botulinum'' production of BoNT is affected by nitrogen and carbon nutrition.<ref>{{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 }}</ref><ref>{{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 }}</ref><ref>{{Cite journal | vauthors = Schantz EJ, Johnson EA |date=1992 |title=Properties and use of botulinum toxin and other microbial neurotoxins in medicine. |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}}</ref> There is evidence that these processes are also under catabolite repression.<ref>{{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 }}</ref>

[[Proteolysis|Proteolytic]] ''Clostridium'' often rely on [[Amino acid|amino acids]] as carbon and energy sources. They carry out a unique metabolic process called [[Stickland fermentation|Stickland Fermentation]].<ref name=":7">{{Cite journal |last1=Hammer |first1=Beth A. |last2=Johnson |first2=Eric A. |date=1988-09-01 |title=Purification, properties, and metabolic roles of NAD+-glutamate dehydrogenase in Clostridium botulinum 113B |journal=Archives of Microbiology |language=en |volume=150 |issue=5 |pages=460–464 |doi=10.1007/BF00422287 |pmid=3061371 |issn=1432-072X}}</ref> In this process, two amino acids are used in complementary roles. One will serve as an [[electron donor]], and the other amino acid serves as an [[electron acceptor]]. Not only does this reaction create precursors for other metabolic pathways, but it also regenerates [[NAD+]],<ref name=":7" /> an important oxidizing agent in the [[Glycolysis|Embden-Meyerhof-Parnas]] pathway. Utilizing amino acids as a carbon source and regenerating NAD+ allows ''C. botulinum'' to thrive in [[anaerobic]] environments.

=== Groups ===
Physiological differences and genome sequencing at 16S [[rRNA]] level support the subdivision of the ''C. botulinum'' species into groups I-IV.<ref name="ScienceDirect 2003 pp. 1407">{{cite book | title=Clostridium | chapter=Clostridium &#124; 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 }}</ref> 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''.<ref name=Smith18/>
{| class="wikitable plainlist"
|+Phenotypic groups of toxin-producing ''Clostridium''<ref name=Dobritsa18/><ref name=Smith18/>
! Property
! Group I
! Group II
! Group III
! ''C. argentinense''
! ''C. baratii''
! ''C. butyricum''
|-
! Proteolysis (casein)
| {{yes|+}}
| {{no|-}}
| {{no|-}}
| {{yes|+}}
| {{no|-}}
| {{no|-}}
|-
! Saccharolysis
| {{no|-}}
| {{yes|+}}
| {{no|-}}
| {{no|-}}
|-
! Lipase
| {{yes|+}}
| {{yes|+}}
| {{yes|+}}
| {{no|-}}
| {{no|-}}
| {{no|-}}
|-
! Toxin Types
| A, B, F
| B, E, F
| C, D
| G
| F
| E
|-
! Toxin gene
| chromosome/plasmid
| chromosome/plasmid
| bacteriophage
| plasmid
| chromosome<ref>{{cite journal | vauthors = Mazuet C, Legeay C, Sautereau J, Bouchier C, Criscuolo A, Bouvet P, Trehard H, Jourdan Da Silva N, Popoff M | title = Characterization of Clostridium Baratii Type F Strains Responsible for an Outbreak of Botulism Linked to Beef Meat Consumption in France | journal = PLOS Currents | volume = 9 | date = February 2017 | pmid = 29862134 | pmc = 5959735 | doi = 10.1371/currents.outbreaks.6ed2fe754b58a5c42d0c33d586ffc606 | doi-broken-date = 11 July 2025 | doi-access = free }}</ref>
| chromosome<ref>{{cite journal | vauthors = Hill KK, Xie G, Foley BT, Smith TJ, Munk AC, Bruce D, Smith LA, Brettin TS, Detter JC | title = Recombination and insertion events involving the botulinum neurotoxin complex genes in Clostridium botulinum types A, B, E and F and Clostridium butyricum type E strains | journal = BMC Biology | volume = 7 | issue = 1 | article-number = 66 | date = October 2009 | pmid = 19804621 | pmc = 2764570 | doi = 10.1186/1741-7007-7-66 | bibcode = 2009BMCB....7...66H | doi-access = free }}</ref>
|-
! Close relatives
|
{{plainlist|1=
* ''[[Clostridium sporogenes|C. sporogenes]]''
* ''C. combesii''
}}
|
* ''C. beijerinckii''
* ''C. butyricum''
|
* ''[[Clostridium novyi|C. novyi]]'' type A
* ''[[Clostridium haemolyticum|C. haemolyticum]]''
| colspan=3 | N/A (already a species)
|}

Although group II cannot degrade native protein such as [[casein]], coagulated [[egg white]], and cooked meat particles, it is able to degrade [[gelatin]].<ref name="Carter Peck 1957 p."/>

Human [[botulism]] is predominantly caused by group I or II ''C. botulinum''.<ref name="Carter Peck 1957 p.">{{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 }}</ref> Group III organisms mainly cause diseases in non-human animals.<ref name="Carter Peck 1957 p."/>

===Laboratory isolation===
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 [[Oxygen scavenger|commercial kits]] that use a chemical reaction to replace O<sub>2</sub> with CO<sub>2</sub>. ''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.<ref name="Doyle">{{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}}</ref>

=== Transmission, sporulation, and germination ===
Sporulation and germination in ''Clostridium botulinum'' is a major [[virulence factor]], allowing the bacteria to be prevalent in a wide variety of environments, and botulism to exist in many forms.<ref name=":6">{{Cite journal |last1=Rossetto |first1=Ornella |last2=Pirazzini |first2=Marco |last3=Montecucco |first3=Cesare |date=August 2014 |title=Botulinum neurotoxins: genetic, structural and mechanistic insights |url=https://www.nature.com/articles/nrmicro3295 |journal=Nature Reviews Microbiology |language=en |volume=12 |issue=8 |pages=535–549 |doi=10.1038/nrmicro3295 |pmid=24975322 |issn=1740-1534|url-access=subscription }}</ref> The exact mechanism behind [[spores|sporulation]] and germination of ''C. botulinum'' is not known, but the study of ''[[Bacillus subtilis|Bacillus subtilus]]'' can be used to give a general prediction of the mechanism.<ref name=":6" /> 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.<ref name=":0">{{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 }}</ref> Within each group, different strains will use different strategies to adapt to their environment to survive.<ref name=":0" /> Unlike other clostridial species, ''C. botulinum'' [[Spore|spores]] will sporulate as it enters the stationary phase.<ref name=":1">{{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 | article-number = 7.6.3 }}</ref> ''C. botulinum'' relies on [[Quorum sensing|quorum-sensing]] to initiate the sporulation process.<ref name=":1" /> ''C. botulinum'' begins sporulation once its sporulation protein becomes phosphorylated.<ref name=":6" /> The [[phosphorylation]] activates the stage I and II sporulation genes that halt [[cell division]], and begin creation of an asymmetric [[septum]] and the spore.<ref name=":6" /> The cell forms spore layers until the spore is fully mature, after which, the cell is covered in [[exosporium]].<ref name=":6" /> Group I cells have a thick yet loose exosporium layer that allows the spore to be heat-resistant, while group III have a thin yet tight exosporium layer that leaves the cell with a moderate amount of heat-resistance.<ref name=":6" /> [[Germination]] will begin if specific nutrients called germinants interact with receptors found within the spore.<ref name=":6" /> Once the germinants are bound to the cell, the cell begins to [[Hydrolysis|hydrolyze]] itself to rehydrate its core and create a vegetative cell.<ref name=":6" /> ''C. botulinum'' spores are not found in human feces unless the individual has contracted botulism,<ref>{{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 }}</ref>  but ''C. botulinum'' cannot spread from person to person.<ref>{{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}}</ref>

=== Motility structures ===
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.<ref name=":4">{{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 }}</ref> When comparing the different strains, there are also differences in the length of the flagella and how many are present on the cell.<ref name=":4" />

Genomic analyses of C. ''botulinum'' have shown many strains to harbor mutations in  flagellar genes, including flaA, which encodes the [[Flagellin|flagellin protein]], and flhA and flgN, which are involved in flagellar [[biosynthesis]]. These mutations can change [[motility]] to varying extents, and in some cases, may modify the structure of the flagellum without fully impairing its function. Flagella are important in colonization and movement in gut environments, but also have immunogenic properties that make the bacterium more visible to host defenses. As a result, strains may downregulating flagellar production or acquire mutations that change flagellar assembly, so they can be used for motility but also evade the immune system during colonization.<ref>{{Cite journal |last1=Douillard |first1=François P. |last2=Derman |first2=Yağmur |last3=Woudstra |first3=Cédric |last4=Selby |first4=Katja |last5=Mäklin |first5=Tommi |last6=Dorner |first6=Martin B. |last7=Saxén |first7=Harri |last8=Dorner |first8=Brigitte G. |last9=Korkeala |first9=Hannu |last10=Lindström |first10=Miia |date=2022-06-28 |title=Genomic and Phenotypic Characterization of Clostridium botulinum Isolates from an Infant Botulism Case Suggests Adaptation Signatures to the Gut |journal=mBio |volume=13 |issue=3 |pages=e0238421 |doi=10.1128/mbio.02384-21 |issn=2150-7511 |pmc=9239077 |pmid=35499308}}</ref>

==Growth conditions and prevention==
{{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.<ref>{{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}}</ref><ref>{{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}}</ref> 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 [[Mesophile|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&nbsp;ng.<ref name="Fleming Biological Safety">{{cite book |title=Biological Safety: principles and practices |vauthors=Fleming DO |publisher=ASM Press |volume=2000 |page=267}}</ref> Botulinum toxin can be destroyed by holding food at 100&nbsp;°C for 10 minutes; however, because of its potency, this is not recommended by the USA's FDA as a means of control.<ref>{{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}}</ref>

Botulism poisoning can occur due to preserved or home-canned, low-acid food that was not processed using correct preservation times and/or pressure.<ref>{{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}}</ref> 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&nbsp;°C (38&nbsp;°F) for type A. For example, in a low-acid, canned vegetable such as [[green bean]]s 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;<ref>{{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 }}</ref> 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 [[Human digestive system|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.<ref>{{cite web |title=Botulism |url=https://www.lecturio.com/concepts/botulism/ |access-date=5 July 2021 |website=The Lecturio Medical Concept Library}}</ref>

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 [[Bacterial growth#Environmental conditions|environmental factors]].
Growth of ''C. botulinum'' is a risk in low acid foods as defined by having a pH above 4.6<ref>{{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 |archive-date=March 24, 2013 |access-date=8 October 2016 |publisher=U.S. Food and Drug Administration}}</ref> although growth is significantly retarded for pH below 4.9.<ref>{{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 }}</ref>

=== Mechanisms of tolerance ===
''C. botulinum'' is very resilient against many mechanisms of [[food processing]] because of the [[Endospore|endospores]] that it produces. These endospores allow the bacteria to survive extreme conditions such as heat, cold, and high or low acidity. These endospores have multiple thick protective layers which allow the bacteria to survive in a dormant state for very long periods of time.<ref name=":5">{{Cite journal |last1=Dahlsten |first1=Elias |last2=Lindström |first2=Miia |last3=Korkeala |first3=Hannu |date=2015-05-01 |title=Mechanisms of food processing and storage-related stress tolerance in Clostridium botulinum |url=https://www.sciencedirect.com/science/article/pii/S0923250814001910 |journal=Research in Microbiology |series=Special issue on Insights into toxigenic Clostridia through genomics |volume=166 |issue=4 |pages=344–352 |doi=10.1016/j.resmic.2014.09.011 |pmid=25303833 |issn=0923-2508|url-access=subscription }}</ref> The endospores can remain dormant in the bacteria, and in this state they are harmless. As endospores [[Germination|germinate]] when they are subject to environments with low oxygen, they multiply producing the neurotoxin that causes botulism.<ref name=":10" /> 

==Taxonomic history==
{{Infobox genome
|image =
|caption =
|term=GCF_000063585.1
|specimen=Sample from str. ATCC 3502
|type=assembly
|ploidy=haploid
|chromosomes=2 (1 plasmid)
|size=3.91 Mb
|year=2007
}}
''C. botulinum'' was first recognized and isolated in 1895 by [[Emile van Ermengem]] from home-cured [[ham]] implicated in a botulism outbreak.<ref>{{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}}</ref> 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.)<ref>{{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 }}</ref> However, isolates from subsequent outbreaks were always found to be [[Anaerobic organism|anaerobic]] spore formers, so [[Ida A. Bengtson]] proposed that both be placed into the genus ''Clostridium'', as the genus ''[[Bacillus]]'' was restricted to [[Aerobic organism|aerobic]] spore-forming rods.<ref>{{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}}</ref>

Since 1959, all species producing the botulinum neurotoxins (types A–G) have been designated ''C. botulinum''. Substantial [[Phenotype|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.<ref name=Uzal>{{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}}</ref><ref name=Smith18>{{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 | article-number = e01469-18 | pmid = 30254123 | pmc = 6156192 | doi = 10.1128/mbio.01469-18 }}</ref>

The situation as of 2018 is as follows:<ref name=Smith18/>

* ''C. botulinum'' type G (= group IV) strains are since 1988 their own species, ''[[Clostridium argentinense|C. argentinense]]''.<ref name=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}}</ref>
* Group I ''C. botulinum'' strains that do not produce a botulin toxin are referred to as ''[[Clostridium sporogenes|C. sporogenes]]''. Both names are [[conserved name]]s since 1999.<ref>{{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 | page = 339 | date = January 1999 | pmid = 10028279 | doi = 10.1099/00207713-49-1-339 | doi-access = free }}</ref> Group I also contains ''[[Clostridium combesii|C. combesii]]''.<ref name="LPSN.combesii">{{cite web |title=Species: Clostridium combesii |url=https://lpsn.dsmz.de/species/clostridium-combesii |website=lpsn.dsmz.de |language=en}}</ref>
* All other botulinum toxin-producing bacteria, not otherwise classified as ''C. baratii'' or ''C. butyricum'',<ref>{{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 | url = https://escholarship.org/uc/item/2r91v270 |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].}}</ref> is called ''C. botulinum''. This group still contains three genogroups.<ref name=Smith18/>

Smith ''et al.'' (2018) argues that group I should be called ''C. parabotulinum'' and group III be called ''[[Clostridium novyi|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.)<ref name=Smith18/> Dobritsa ''et al.'' (2018) argues, without  formal descriptions, that group II can potentially be made into two new species.<ref name=Dobritsa18>{{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 }}</ref>

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.<ref>{{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}}</ref>

== Diagnosis ==
Physicians may consider the diagnosis of botulism based on a patient's clinical presentation, which classically includes an acute onset of bilateral [[Cranial neuropathy|cranial neuropathies]] and symmetric descending weakness.<ref name="pmid9585323">{{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 }}</ref><ref>{{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 }}</ref> 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.<ref>{{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|archive-url=https://web.archive.org/web/20161005200323/https://www.cdc.gov/botulism/testing-treatment.html|url-status=dead|archive-date=5 October 2016}}</ref><ref>{{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}}</ref> 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]].<ref>{{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 }}</ref> 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.<ref>{{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 }}</ref>
* '''Wound botulism:''' isolation of ''C. botulinum'' from the wound site should be attempted, as growth of the bacteria is diagnostic.<ref>{{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 }}</ref>
* '''Adult enteric and infant botulism:''' isolation and growth of ''C. botulinum'' from stool samples is diagnostic.<ref>{{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 | bibcode = 1981JCMb...13..526D }}</ref> Infant botulism is a diagnosis which is often missed in the emergency room.<ref name=":2">{{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 }}</ref>

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).<ref>{{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 }}</ref>
* Collection of [[cerebrospinal fluid]] (CSF) protein and blood assist with the exclusion of [[Guillain–Barré syndrome|Guillan-Barre syndrome]] and [[stroke]].<ref>{{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 }}</ref>
* Detailed physical examination of the patient for any rash or tick presence helps with the exclusion of any tick transmitted tick paralysis.<ref>{{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 }}</ref>

== Pathology ==

=== Foodborne botulism ===
Signs and symptoms of foodborne botulism typically begin between 18 and 36 hours after the toxin gets into the body, but can range from a few hours to several days, depending on the amount of toxin ingested. Symptoms include:<ref>{{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 | page = 509 | date = August 2020 | pmid = 32784744 | pmc = 7472133 | doi = 10.3390/toxins12080509 | doi-access = free }}</ref><ref name="mayosymptoms">{{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]]}}</ref>
* Double vision
* Blurred vision
* [[Ptosis (eyelid)|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

===Wound botulism===
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.<ref>{{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}}</ref> Wound botulism signs and symptoms include:<ref name="mayosymptoms" /><ref>{{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 | article-number = 103 | date = October 2017 | pmid = 29073888 | pmc = 5658925 | doi = 10.1186/s12893-017-0300-4 | doi-access = free }}</ref>
* Difficulty swallowing or speaking
* Facial weakness on both sides of the face
* Blurred or double vision
* Ptosis
* Trouble breathing
* Paralysis

===Infant botulism===
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:<ref name=":2" /><ref name="mayosymptoms" />
* 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<ref name="mayosymptoms" />

===Beneficial effects of botulinum toxin===
Purified botulinum toxin is diluted by a physician for treatment of:<ref>{{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}}</ref>
* 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<ref name="Arnon SS 2001">{{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 }}</ref>

===Adult intestinal toxemia===
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:<ref>{{cite journal | vauthors = Harris RA, Anniballi F, Austin JW | title = Adult Intestinal Toxemia Botulism | journal = Toxins | volume = 12 | issue = 2 | page = 81 | date = January 2020 | pmid = 31991691 | pmc = 7076759 | doi = 10.3390/toxins12020081 | doi-access = free }}</ref>
* Abdominal pain
* Blurred vision
* Diarrhea
* [[Dysarthria]]
* Imbalance
* Weakness in arms and hand area<ref>{{cite web | title = Botulism | url = https://www.cdc.gov/botulism/index.html | work = Centers for Disease Control and Prevention | access-date  = 23 October 2016 }}</ref>

=== Veterinary pathology ===
Most cases of botulism in animals come from foodborne botulism, though wound botulism is also common.<ref name=":9">{{Cite journal |last1=Anniballi |first1=Fabrizio |last2=Fiore |first2=Alfonsina |last3=Löfström |first3=Charlotta |last4=Skarin |first4=Hanna |last5=Auricchio |first5=Bruna |last6=Woudstra |first6=Cédric |last7=Bano |first7=Luca |last8=Segerman |first8=Bo |last9=Koene |first9=Miriam |last10=Båverud |first10=Viveca |last11=Hansen |first11=Trine |last12=Fach |first12=Patrick |last13=Åberg |first13=Annica Tevell |last14=Hedeland |first14=Mikael |last15=Engvall |first15=Eva Olsson |date=September 2013 |title=Management of Animal Botulism Outbreaks: From Clinical Suspicion to Practical Countermeasures to Prevent or Minimize Outbreaks |url=https://www.liebertpub.com/doi/10.1089/bsp.2012.0089 |journal=Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science |volume=11 |issue=S1 |pages=S191–S199 |doi=10.1089/bsp.2012.0089 |pmid=23971806 |issn=1538-7135}}</ref> Foodborne botulism comes from ingestion of infected material, like raw or decaying vegetation, carcasses, or larvae that have consumed infected material.<ref name=":9" /> Ruminants have longer incubation times for foodborne botulism when compared to animals with less complex stomachs.<ref name=":9" /> Wound botulism occurs when a wound becomes infected with Clostridium botulinum that is allowed to germinate and produce toxins. <ref name=":9" />

Toxicoinfection can also cause botulism cases as Clostridium botulinum cells infect the lower intestine and begin to produce toxins.<ref name=":9" /> The toxin is either expelled as feces from the animal, not causing any harm but spreading the toxin, or, if in close proximity to the beginning of the small intestine, causes symptoms to present in the host.<ref name=":9" /> 

Botulism symptoms in cattle and horses can begin with weakness or trembling in the hindquarters which progresses into full body paralysis and eventually death.<ref name=":9" /> Avian botulism is characterized by the inability of the animal to fly, walk, lift its neck, or close its inner eyelid, followed by death.<ref name=":9" /> Small carnivores, like foxes, mink, and ferrets, are prone to botulism and will present flaccid paralysis, then die.<ref name=":9" /> An infected fish will have each of its fins paralyzed over time until the tail fin is fully paralyzed, preventing swimming, killing the fish.<ref name=":9" />

== Treatment ==
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.<ref>{{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 }}</ref><ref>{{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 }}</ref><ref>{{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 }}</ref>

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.<ref>{{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 }}</ref><ref>{{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}}</ref>

Outcomes vary between one and three months, but with prompt interventions, mortality from botulism ranges from less than 5 percent to 8 percent.<ref>{{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 =  }}</ref>

Despite these interventions, there is currently no approved pharmacological treatment that reverses botulinum neurotoxin once it has entered [[Neuron|neurons]]. Due to this limitation, early antitoxin administration and supportive care is critical. Ongoing research investigates several therapeutic strategies; for example, recombinant vaccines based on the heavy-chain (HC) domains of BoNTs have provided protective immunity in animals and shown promise in early clinical trials. However, no human vaccine is currently licensed. Veterinary vaccines are available to prevent outbreaks in livestock.<ref name=":8">{{Cite journal |last1=Rossetto |first1=Ornella |last2=Pirazzini |first2=Marco |last3=Montecucco |first3=Cesare |date=August 2014 |title=Botulinum neurotoxins: genetic, structural and mechanistic insights |url=https://www.nature.com/articles/nrmicro3295 |journal=Nature Reviews Microbiology |language=en |volume=12 |issue=8 |pages=535–549 |doi=10.1038/nrmicro3295 |pmid=24975322 |issn=1740-1534|url-access=subscription }}</ref>

Antibody-based therapies are also under development. Traditional equine antitoxins, though effective, carry risks of serum sickness. Human [[polyclonal antibodies]] isolated from immunized volunteers and novel camelid [[Single-domain antibody|single-domain antibodies]] are two alternatives, which may provide safer and longer-lasting protection. Additionally, small-molecule inhibitors targeting the metalloprotease activity of the toxin’s light chain are being explored as potential post-exposure therapies.<ref name=":8" />

Clinical outcomes also depend on the toxin [[serotype]] involved. Type A toxins typically cause the most prolonged paralysis, while type E toxins are associated with shorter disease courses. Although BoNTs induce paralysis, they do not destroy neurons; with adequate ventilation and intensive care, patients can fully recover as [[nerve]] terminals regenerate.<ref name=":8" />

Due to the extreme potency of botulinum [[Neurotoxin|neurotoxins]], much of this therapeutic research is framed in context of biodefense preparedness against the potential use of BoNTs as biological weapons.<ref name=":8" />

== Vaccination ==
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.<ref>{{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 }}</ref>

== Use and detection ==
''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]].<ref>{{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 }}</ref>

[[Botulin toxin|Botulinum toxin]] produced by ''C. botulinum'' is often believed to be a potential [[bioweapon]] as it is so potent that it takes about 75 [[nanogram]]s to kill a person ({{LD50}} of 1&nbsp;ng/kg,<ref name="Fleming Biological Safety" /> assuming an average person weighs ~75&nbsp;kg); 1&nbsp;kilogram of it would be enough to kill the [[world population|entire human population]].

A "mouse protection" or "mouse [[bioassay]]" test determines the type of ''C. botulinum'' toxin present using [[monoclonal antibody|monoclonal antibodies]]. An enzyme-linked [[immunosorbent assay]] ([[ELISA]]) with [[digoxigenin]]-labeled antibodies can also be used to detect the toxin,<ref>{{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 }}</ref> and [[quantitative PCR]] can detect the toxin genes in the organism.<ref name="Satterfield, B. A. 2010" />

==''C. botulinum'' in different geographical locations==
A number of [[Numerical data|quantitative]] [[Statistical survey|surveys]] for ''C. botulinum'' [[spores]] in the environment have suggested a prevalence of specific toxin types in given geographic areas, which remain unexplained.
{| class="wikitable"
|+
!Location
!
|-
|North America
|Type A ''C. botulinum'' predominates the [[soil]] samples from the western regions, while type B is the major type found in eastern areas.<ref name="Hauschild_1989">{{cite book | vauthors = Hauschild AH | date = 1989 | chapter = Clostridium botulinum. | veditors = Doyle MP | title = Food-borne Bacterial Pathogens. | publisher = Marcel Dekker | location = New York | pages = 111–189 }}</ref> The type-B organisms were of the proteolytic Group I. [[Sediments]] from the [[Great Lakes]] region were surveyed after outbreaks of botulism among commercially reared [[fish]], and only type E spores were detected.<ref name="pmid4870273">{{cite journal | vauthors = Bott TL, Johnson J, Foster EM, Sugiyama H | title = Possible origin of the high incidence of Clostridium botulinum type E in an inland bay (Green Bay of Lake Michigan) | journal = Journal of Bacteriology | volume = 95 | issue = 5 | pages = 1542–7 | date = May 1968 | pmid = 4870273 | pmc = 252172 | doi = 10.1128/jb.95.5.1542-1547.1968 }}</ref><ref>{{cite journal | vauthors = Eklund MW, Peterson ME, Poysky FT, Peck LW, Conrad JF | title = Botulism in juvenile coho salmon (Oncorhynchus kisutch) in the United States. | journal = Aquaculture | date = February 1982 | volume = 27 | issue = 1 | pages = 1–11 | doi = 10.1016/0044-8486(82)90104-1 | bibcode = 1982Aquac..27....1E }}</ref><ref>{{cite journal | vauthors = Eklund MW, Poysky FT, Peterson ME, Peck LW, Brunson WD | title = Type E botulism in salmonids and conditions contributing to outbreaks. | journal = Aquaculture | date = October 1984 | volume = 41 | issue = 4 | pages = 293–309 | doi = 10.1016/0044-8486(84)90198-4 | bibcode = 1984Aquac..41..293E }}</ref> In a survey, type-A strains were isolated from soils that were [[Neutral solution|neutral]] to [[alkaline]] (average pH 7.5), while type-B strains were isolated from slightly [[acidic]] soils (average pH 6.23).
|-
|Europe
|''C. botulinum'' type E is prevalent in aquatic sediments in [[Norway]] and [[Sweden]],<ref>{{cite journal | vauthors = Johannsen A | title = Clostridium botulinum in Sweden and the adjacent waters. | journal = Journal of Applied Bacteriology | date = April 1963 | volume = 26 | issue = 1 | pages = 43–47 | doi = 10.1111/j.1365-2672.1963.tb01153.x }}</ref> [[Denmark]],<ref name="pmid6990867">{{cite journal | vauthors = Huss HH | title = Distribution of Clostridium botulinum | journal = Applied and Environmental Microbiology | volume = 39 | issue = 4 | pages = 764–9 | date = April 1980 | pmid = 6990867 | pmc = 291416 | doi = 10.1128/aem.39.4.764-769.1980 | bibcode = 1980ApEnM..39..764H }}</ref> the [[Netherlands]], the Baltic coast of [[Poland]], and [[Russia]].<ref name="Hauschild_1989"/> The type-E ''C. botulinum'' was suggested to be a true [[Aquatic ecosystem|aquatic]] organism, which was indicated by the correlation between the level of type-E contamination and flooding of the land with seawater. As the land dried, the level of type E decreased and type B became dominant.<ref>{{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 }}</ref>
In soil and sediment from the United Kingdom, ''C. botulinum'' type B predominates. In general, the incidence is usually lower in soil than in [[sediment]]. In Italy, a survey conducted in the vicinity of [[Rome]] found a low level of contamination; all strains were [[Proteolysis|proteolytic]] (Group I) ''C. botulinum'' types A or B.<ref>{{cite journal | vauthors =  Creti R, Fenicia J, Aureli P |date=May 1990 |title=Occurrence of Clostridium botulinum in the soil of the vicinity of Rome |journal=Current Microbiology |volume=20 |issue=5 |pages=317–321 |doi=10.1007/bf02091912}}</ref>
|-
|Australia
|''C. botulinum'' type A was found to be present in soil samples from mountain areas of [[Victoria (Australia)|Victoria]].<ref>{{cite journal | vauthors = Eales CE, Gillespie JM | title = The isolation of Clostridium botulinum type A from Victorian soils | journal = The Australian Journal of Science | volume = 10 | issue = 1 | page = 20 | date = August 1947 | pmid = 20267540 }}</ref> Type-B organisms were detected in marine mud from [[Tasmania]].<ref>{{cite journal | vauthors = Ohye DF, Scott WJ |date=1957 |title=Studies in the physiology of ''Clostridium botulinum'' type E |journal=Australian Journal of Biological Sciences |url=https://www.publish.csiro.au/bi/pdf/bi9570085 |volume=10 |pages=85–94 |doi=10.1071/BI9570085}}</ref> Type-A ''C. botulinum'' has been found in [[Sydney]] suburbs and types A and B were isolated from [[Urban area|urban]] areas. In a well-defined area of the [[Darling Downs|Darling-Downs]] region of [[Queensland]], a study showed the prevalence and persistence of ''C. botulinum'' type B after many cases of botulism in [[horse]]s.
|}

== References ==
{{notelist}}
{{Reflist}}<ref name=":10">{{Citation |last1=Basta |first1=Marina |title=Bacterial Spores |date=2025 |work=StatPearls |url=http://www.ncbi.nlm.nih.gov/books/NBK556071/ |access-date=2025-11-13 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32310531 |last2=Annamaraju |first2=Pavan}}</ref>

== Further reading ==
{{refbegin}}
* {{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 | bibcode = 2005CliID..41.1167S | doi-access = free }}
{{refend}}

== External links ==
{{Toxins}}
{{Gram-positive firmicutes diseases}}
{{Taxonbar|from=Q131268}}
{{Authority control}}

[[Category:Bacteria described in 1896]]
[[Category:Botulism]]
[[Category:Clostridium|botulinum]]
[[Category:Food microbiology]]
[[Category:Gram-positive bacteria]]
[[Category:Pathogenic bacteria]]