Editing Clostridium botulinum (section)

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

==== Toxin types in disease ====
Only [[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 | pages = 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'' had 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" />