Clostridium botulinum: Difference between revisions

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#REDIRECT [[Botulism]]
{{Taxobox
| name = ''Clostridium botulinum''
| image = Clostridium botulinum_01.png
| image_width = 240px
| image_caption = ''Clostridium botulinum'' stained with [[gentian violet]].
| domain = [[Bacteria]]
| classis = [[Clostridia]]
| ordo = [[Clostridia]]les
| familia = [[Clostridiaceae]]
| genus = ''[[Clostridium]]''
| species = '''''C. botulinum'''''
| binomial = ''Clostridium botulinum''
| binomial_authority = van Ermengem, 1896
}}
 
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{{About0|Botulism}}
{{Botulism}}
{{CMG}}
 
'''''Clostridium botulinum''''' is a [[Gram-positive bacteria|Gram-positive]], rod-shaped, [[Anaerobic organism|anaerobic]], spore-forming, motile [[bacterium]] with the ability to produce the neurotoxin [[Botulinum toxin|botulinum]].<ref name="Peck">{{cite journal|last=Peck|first=MW|title=Biology and genomic analysis of Clostridium botulinum|journal=Advances in microbial physiology|date=2009|volume=55|pages=183–265, 320|pmid=19573697|doi=10.1016/s0065-2911(09)05503-9|series=Advances in Microbial Physiology|isbn=9780123747907}}</ref><ref name="Lindström">{{cite journal|last=Lindström|first=M|author2=Korkeala, H|title=Laboratory diagnostics of botulism.|journal=Clinical Microbiology Reviews|date=Apr 2006|volume=19|issue=2|pages=298–314|pmid=16614251|doi=10.1128/cmr.19.2.298-314.2006|pmc=1471988}}</ref>  The botulinum toxin can cause a severe [[Flaccid paralysis|flaccid paralytic]] disease in humans and animals<ref name="Lindström" /> and is the most potent toxin known to humankind, natural or synthetic, with a lethal dose of 1.3-2.1ng/kg in humans.<ref name=":0">(2010). Chapter 29. Clostridium, Peptostreptococcus, Bacteroides, and Other Anaerobes. In Ryan K.J., Ray C (Eds), ''Sherris Medical Microbiology'', 5th ed. ISBN 978-0071604024</ref>
 
''C. botulinum'' is a diverse group of bacteria initially grouped together by their ability to produce botulinum toxin and now known as four distinct groups, ''C. botulinum'' groups I-IV.  ''C. botulinum'' groups I-IV, as well as some strains of ''Clostridium butyricum'' and ''Clostridium baratii'', are the bacteria responsible for producing botulinum toxin.<ref name=Peck />
 
''C. botulinum'' is responsible for foodborne 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 allow for survival in adverse conditions.<ref name=Peck />
 
==Microbiology==
 
''C. botulinum ''is a [[Gram-positive bacteria|Gram-positive]], rod-shaped, spore-forming [[bacterium]].  It is an [[obligate anaerobe]], meaning that [[oxygen]] is poisonous to the cells. 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 | author = Doyle, Michael P. | title = Food Microbiology: Fundamentals and Frontiers | publisher = ASM Press| year = 2007 | isbn = 1-55581-208-2 }}</ref> ''C. botulinum'' is only able to produce the neurotoxin during sporulation, which can only happen in an anaerobic environment.  Other bacterial species produce spores in an unfavorable growth environment to preserve the organism's viability and permit survival in a dormant state until the spores are exposed to favorable conditions.
 
''C. botulinum ''is divided in to 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 | last1 = Peck | first1 = MW | last2 = Stringer | first2 = SC | last3 = Carter | first3 = AT. | year = 2011 | title = Clostridium botulinum in the post-genomic era | url = | journal = Food Microbiol | volume = 28 | issue = 2| pages = 183–91 | doi = 10.1016/j.fm.2010.03.005 | pmid = 21315972 }}</ref><ref>{{cite journal | last1 = Shukla | first1 = HD | last2 = Sharma | first2 = SK. | year = 2005 | title = Clostridium botulinum: a bug with beauty and weapon | url = | journal = Crit Rev Microbiol | volume = 31 | issue = 1| pages = 11–8 | doi = 10.1080/10408410590912952 | pmid = 15839401 }}</ref>  Recently, an eighth serotype (H) has been described.<ref name=":1">{{cite web |url=http://www.newscientist.com/article/dn24398-new-botox-supertoxin-has-its-details-censored.html |title=New botox super-toxin has its details censored |last1= MacKenzie|first1= Debora|date=14 October 2013 |website=NewScientist |accessdate=15 October 2013}}</ref>
 
=== Groups ===
The classification into groups is based on the ability of the organism to [[digestion|digest]] complex [[proteins]].<ref>L. V. Holdeman, J. B. Brooks. 1970. Variation among strains of Clostridium botulinum  and related clostridia. Protocols of the first U.S-Japan conference on Toxic Microorganisms. pp. 278–286</ref><ref>L. D. S. Smith, G. Hobbs. 1974. Genus III Clostridium Prazmowski 1880, 23. In R. E. Buchanan, N. E. gibbons (eds.), ''Bergey’s Manual of Determinative Bacteriology'', 8th ed. William & Wilkins, Baltimore. pp. 551–572. ISBN 978-0683006032</ref> Studies at the [[DNA]] and [[rRNA]] level support the subdivision of the species into groups I-IV. Most outbreaks of human [[botulism]] are caused by group I (proteolytic) or II (non-proteolytic) ''C. botulinum''. Group III organisms mainly cause diseases in animals. Group IV ''C. botulinum'' has not been shown to cause human or animal disease.
 
=== Botulinum toxin ===
[[Neurotoxin]] production is the unifying feature of the species. Eight types of [[toxins]] have been identified (including the recently described type H) that are allocated a letter (A-H).<ref name=":1" />  All toxins are rapidly destroyed at 100°C, but they are resistant to degradation by enzymes found in the gastrointestinal tract. This allows for ingested toxin to be absorbed from the intestines into the bloodstream.<ref name=":0" />
 
Most strains produce one type of [[neurotoxin]], 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 | last1 = Hatheway | first1 = C. L. | last2 = McCroskey | first2 = L. M. | year = 1987 | title = Examination of faeces for diagnosis of infant botulism in 336 patients | url = | journal = J. Clin. Microbiol | volume = 25 | issue = 12| pages = 2334–2338 | pmid = 3323228 | pmc = 269483 }}</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. Evidence indicates the neurotoxin genes have been the subject of [[horizontal gene transfer]], possibly from a viral 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, indicating that the ''C. botulinum'' acquired the toxin genes quite far in the evolutionary past.
 
==== Botulinum toxin types ====
Only [[botulinum toxin]] types A, B, E, F, and H cause disease in humans.  Types A, B, and E are associated with foodborne illness, with type E specifically associated with fish products. Type C produces limberneck in birds and type D causes botulism in other mammals.  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 978-0071790314</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 | doi = 10.1099/jmm.0.012567-0 | last1 = Satterfield | first1 = B. A. | last2 = Stewart | first2 = A. F. | last3 = Lew | first3 = C. S. | last4 = Pickett | first4 = D. O. | last5 = Cohen | first5 = M. N. | last6 = Moore | first6 = E. A. | last7 = Luedtke | first7 = P. F. | last8 = O'Neill | first8 = K. L. | last9 = Robison | first9 = R. A. et al. | year = 2010 | title = A quadruplex real-time PCR assay for rapid detection and differentiation of the Clostridium botulinum toxin genes A, B, E and F | journal = J Med Microbiol | volume = 59 | issue = Pt 1| pages = 55–64 | pmid = 19779029 | display-authors = 9 | author10 = and others }}</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 | last1 = Aureli | first1 = P. | last2 = Fenicia | first2 = L. | last3 = Pasolini | first3 = B. | last4 = Gianfrancesche | first4 = M. | last5 = Mccroskey | first5 = J. M. | last6 = Hatheway | first6 = C. L. | year = 1986 | title = Two cases of type E infant botulism caused by neurotoxigenic Clostridium botulinum in Italy | url = | journal = J. Infect. Dis. | volume = 154 | issue = 2| pages = 207–211 | pmid = 3722863 | doi=10.1093/infdis/154.2.207}}</ref> and ''C. baratii'' had produced type F toxin.<ref>{{cite journal | last1 = Hall | first1 = J. D. | last2 = McCroskey | first2 = L. M. | last3 = Pincomb | first3 = B. J. | last4 = Hatheway | first4 = C. L. | year = 1985 | title = Isolation of an organism resembling Clostridium baratii which produces a type F botulinal toxin from an infant with botulism | url = | journal = J. Clin. Microbiol | volume = 21 | issue = 4| pages = 654–655 | pmid = 3988908 | pmc = 271744 }}</ref><ref>{{cite journal | doi = 10.1007/BF00395840 | last1 = Notermans | first1 = S. | last2 = Havellar | first2 = A. H. | year = 1980 | title = Removal and inactivation of botulinum toxin during production of drinking water from surface water | url = | journal = Antonie van Leeuwenhoek | volume = 46 | issue = 5| pages = 511–514 }}</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.
 
An eighth toxin, type H, was discovered by researchers at the [[California Department of Public Health]] in 2013. With a lethal dose of 2 [[nanogram|ng]] by injection or 13&nbsp;ng by inhalation, it was deemed the most toxic substance on Earth.<ref name=":1" />
 
{| class="wikitable" style="text-align: center;" rules="all"
|+
Phenotypic groups of ''Clostridium botulinum''
 
! style="background-color: #0099CC; color: #fef;" |
Properties
! style="background-color: #0099CC; color: #fff;" |
Group I
! style="background-color: #0099CC; color: #fff;" |
Group II
! style="background-color: #0099CC; color: #fff;" |
Group III
! style="background-color: #0099CC; color: #fff;" |
Group IV
|-
! style="background-color: #CCFFFF; color: #000000;" |
Toxin Types
| style="background-color: #CCFFFF; color: #006000;" | A, B, F
| style="background-color: #CCFFFF; color: #000000;" | B, E, F
| style="background-color: #CCFFFF; color: #000000;" | C, D
| style="background-color: #CCFFFF; color: #000000;" | G
|-
! style="background-color: #CCFFFF; color: #000000;" |
Proteolysis
| style="background-color: #CCFFFF; color: #000000;" | +
| style="background-color: #CCFFFF; color: #000000;" | -
| style="background-color: #CCFFFF; color: #000000;" | weak
| style="background-color: #CCFFFF; color: #000000;" | -
|-
! style="background-color: #CCFFFF; color: #000000;" |
Saccharolysis
| style="background-color: #CCFFFF; color: #000000;" | -
| style="background-color: #CCFFFF; color: #000000;" | +
| style="background-color: #CCFFFF; color: #000000;" | -
| style="background-color: #CCFFFF; color: #000000;" | -
|-
! style="background-color: #CCFFFF; color: #050000;" |
Disease host
| style="background-color: #CCFFFF; color: #000000;" | human
| style="background-color: #CCFFFF; color: #000000;" | human
| style="background-color: #CCFFFF; color: #000000;" | animal
| style="background-color: #CCFFFF; color: #000000;" | -
|-
! style="background-color: #CCFFFF; color: #000000;" |
Toxin gene
| style="background-color: #CCFFFF; color: #000000;" | chromosome/plasmid
| style="background-color: #CCFFFF; color: #000000;" | chromosome/plasmid
| style="background-color: #CCFFFF; color: #000000;" | bacteriophage
| style="background-color: #CCFFFF; color: #000000;" | plasmid
|-
! style="background-color: #CCFFFF; color: #000000;" |
Close relatives
| style="background-color: #CCFFFF; color: #000000;" | ''C. sporogenes'', ''C. putrificum''
| style="background-color: #CCFFFF; color: #000000;" | ''C. butyricum'', ''[[Clostridium beijerinckii|C. beijerinickii]]''
| style="background-color: #CCFFFF; color: #000000;" | ''C. haemolyticum'', ''C. novyi type A''
| style="background-color: #CCFFFF; color: #000000;" | ''C. subterminale'', ''C. haemolyticum''
|}
 
====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 commercial kits that use a chemical reaction to replace O<sub>2</sub> with CO<sub>2</sub>. ''C. botulinum'' 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 | author = . | title = Brock Biology of Microorganisms | edition = 11th | publisher = Prentice Hall | year = 2005 |isbn = 0-13-144329-1 }}</ref>
 
==Taxonomy history==
''C. botulinum'' was first recognized and isolated in 1895 by [[Emile van Ermengem]] from home-cured [[ham]] implicated in a botulism outbreak.<ref>E. van Ergmengem. 1897. Über einen neuen anaeroben Bacillus und seine Beziehungen Zum Botulismus. Zentralbl. Hyg. Infektionskr. 26:1–8.</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>Frank J. Erbguth. Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin. ''Movement Disorders''. Volume 19, Issue S8, pages S2-S6, March 2004.</ref> However, isolates from subsequent outbreaks were always found to be [[Anaerobic organism|anaerobic]] spore formers, so [[Ida A. Bengtson]] proposed that the organism be placed into the genus ''Clostridium'', as the ''[[Bacillus]]'' genus was restricted to [[Aerobic organism|aerobic]] spore-forming rods.<ref>I. A. Bengston. 1924. Studies on organisms concerned as causative factors in botulism. Hyg. Lab. Bull. 136:101</ref>
 
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]]. This has led to the reclassification of ''C. botulinum'' type G strains as a new species, ''C. argentinense''.<ref>J. C. Suen, C. L. Hatheway, A. G. Steigerwalt, D. J. Brenner. 1988, Clostridium argentinense sp.nov.: a genetically homogeneous group composed of all strains of Clostridium botulinum type G and some nontoxigenic strains previously identified as Clostridium subterminale or Clostridium hastiforme. Int. J. Sys. Bacteriol. 38:375–381.</ref>
 
Group I ''C. botulinum'' strains that do not produce a botulin toxin are referred to as ''[[Clostridium sporogenes|C. sporogenes]]''.<ref>Judicial Commission of the International Committee on Systematic Bacteriology (1999) Rejection of ''Clostridium putrificum'' and conservation of ''Clostridium botulinum'' and ''Clostridium sporogenes'' Opinion 69. International Journal of Systematic Bacteriology. 49:339.</ref>
 
The complete genome of ''C. botulinum'' has been sequenced at Sanger.<ref>http://www.sanger.ac.uk/Projects/C_botulinum/</ref>
 
==''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.
 
===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">A. H. W. Hauschild. 1989. Clostridium botulinum. In M. P. Doyle (ed.), Food-borne Bacterial Pathogens. Marcel Dekker, New York. Pp. 111–189</ref> The type-B organisms were of the proteolytic type I. [[Sediments]] from the [[Great Lake]]s region were surveyed after outbreaks of botulism among commercially reared [[fish]], and only type E spores were detected.<ref>{{cite journal | last1 = Bott | first1 = T. L. | last2 = Johnson | first2 = J. | last3 = Foster | first3 = E. M. | last4 = Sugiyama | first4 = H. | year = 1968 | title = Possible origin of the fish incidences of Clostridium botulinum type E in an inland bay (Green Bay of Lake Michigan) | url = | journal = J. Bacteriol | volume = 95 | issue = | page = 1542 }}</ref><ref>M. W. Eklund, M. E. Peterson, F. T. Poysky, L. W. Peck, J. F. Conrad. 1982. Botulism in juvenile Coho salmon (Onocorhynchus kisutch) in the United States. Aquaculture 27:1–11</ref><ref>M. W. Eklund, F. T. Poysky M. E. Peterson, L. W. Peck, Brunson. 1984. Type E botulism in salmonids and conditions contributing to outbreaks. Aquaculture 41:293–309.</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 6.25).
 
===Europe===
''C. botulinum'' type E is prevalent in aquatic sediments in [[Norway]] and [[Sweden]],<ref>A. Johannsen. 1963. Clostridium botulinum  in Sweden and the adjacent waters. J. Appl. Bacteriol. 26:43–47.</ref> [[Denmark]],<ref>{{cite journal | last1 = Huss | first1 = H. H. | year = 1980 | title = Distribution of Clostridium botulinum | url = | journal = Appl. Environ. Microbiol | volume = 39 | issue = 4| pages = 764–769 | pmid = 6990867 | pmc = 291416 }}</ref> the [[Netherlands]], the [[Baltic Sea|Baltic]] coast of [[Poland]], and [[Russia]].<ref name=" Hauschild "/> 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.
 
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 proteolytic ''C. botulinum'' types A or B.<ref>{{cite journal | last1 = Creti | first1 = R. | last2 = Fenicia | first2 = J. | last3 = Aureli | first3 = P. | year = 1990 | title = Occurrence of Clostridium botulinum in the soil of the vicinity of Rome | url = | journal = Curr. Microbiol | volume = 20 | issue = 5| page = 317 | 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 | last1 = Eales | first1 = C. E. | last2 = Gillespie | first2 = J. M. | year = 1947 | title = the isolation of Clostridium botulinum type A from Victorian soils. Aust. J | url = | journal = Sci | volume = 10 | issue = | pages = 20–21 }}</ref> Type-B organisms were detected in marine mud from [[Tasmania]].<ref>{{cite journal | last1 = Ohye | first1 = W. J. Scott | year = 1957 | title = Studies in the physiology of Clostridium botulinum type E. Aust. L. Biol | url = | journal = Sci | volume = 10 | issue = | pages = 85–94 }}</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 region of [[Queensland]], a study showed the prevalence and persistence of ''C. botulinum'' type B after many cases of botulism in [[horse]]s.
 
== Other ==
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>Shashi K. Sharma, Joseph. L. Ferreira, Brian S. Eblen and Richard C. Whitingand. 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. Appl. Environ. Microbiol. February 2006 vol. 72 no. 2 1231-1238. {{doi|10.1128/AEM.72.2.1231-1238.2006}}</ref> and [[quantitative PCR]] can detect the toxin genes in the organism.<ref name="Satterfield, B. A. 2010"/>
 
''C. botulinum'' is also 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]].
 
[[Botulin 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>{{cite journal | last1 = Fleming | first1 = Diane O. | title = Biological Safety: principles and practices | url = | journal = ASM Press | volume = 2000 | issue = | page = 267 }}</ref> assuming an average person weighs ~75&nbsp;kg); 1&nbsp;kilogram of it would be enough to kill the [[world population|entire human population]]. For comparative purposes, a quarter of a typical grain of sand's weight (350&nbsp;ng) of botulinum toxin would constitute a lethal dose for humans.
 
''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.
 
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 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; 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.
 
 
 
==Gallery==
 
<gallery>
 
Image: Botulism15.jpeg| Violet-stained culture specimen revealing the presence of numerous Gram-positive Clostridium botulinum. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
 
Image: Botulism14.jpeg| Photomicrograph of Clostridium botulinum type A. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
 
Image: Botulism13.jpeg| Photomicrograph of Clostridium botulinum type A. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
</gallery>
==References==
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==External links==
*[http://pathema.jcvi.org/cgi-bin/Clostridium/PathemaHomePage.cgi Pathema-''Clostridium'' Resource]
*{{cite journal|doi=10.1086/444507|author=Jeremy Sobel|journal=Clinical Infectious Diseases|volume=41|issue=8|pages=1167–1173|title=Botulism|year=2005|pmid=16163636}}
*[http://www.ifr.ac.uk/info/science/FoodbornePathogens/Cbotulinum.htm Current research on ''Clostridium botulinum'' at the Norwich Research Park]
 
{{Gram-positive bacterial diseases}}
 
{{Authority control}}
{{DEFAULTSORT:Clostridium Botulinum}}
[[Category:Bacteria]]
[[Category:Clostridiaceae]]
[[Category:Gram-positive bacteria]]
[[Category:Neurotoxins]]
[[Category:Botulism]]

Revision as of 20:10, 6 August 2015

style="background:#Template:Taxobox colour;"|Clostridium botulinum
File:Clostridium botulinum 01.png
Clostridium botulinum stained with gentian violet.
style="background:#Template:Taxobox colour;" | Scientific classification
Domain: Bacteria
Class: Clostridia
Order: Clostridiales
Family: Clostridiaceae
Genus: Clostridium
Species: C. botulinum
Binomial name
Clostridium botulinum
van Ermengem, 1896


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Clostridium botulinum is a Gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce the neurotoxin botulinum.[1][2] The botulinum toxin can cause a severe flaccid paralytic disease in humans and animals[2] and is the most potent toxin known to humankind, natural or synthetic, with a lethal dose of 1.3-2.1ng/kg in humans.[3]

C. botulinum is a diverse group of bacteria initially grouped together by their ability to produce botulinum toxin and now known as four distinct groups, C. botulinum groups I-IV. C. botulinum groups I-IV, as well as some strains of Clostridium butyricum and Clostridium baratii, are the bacteria responsible for producing botulinum toxin.[1]

C. botulinum is responsible for foodborne 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 endospores that are commonly found in soil and allow for survival in adverse conditions.[1]

Microbiology

C. botulinum is a Gram-positive, rod-shaped, spore-forming bacterium. It is an obligate anaerobe, meaning that oxygen is poisonous to the cells. 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.[4] C. botulinum is only able to produce the neurotoxin during sporulation, which can only happen in an anaerobic environment. Other bacterial species produce spores in an unfavorable growth environment to preserve the organism's viability and permit survival in a dormant state until the spores are exposed to favorable conditions.

C. botulinum is divided in to four distinct phenotypic groups (I-IV) and is also classified into seven serotypes (A-G) based on the antigenicity of the botulinum toxin produced.[5][6] Recently, an eighth serotype (H) has been described.[7]

Groups

The classification into groups is based on the ability of the organism to digest complex proteins.[8][9] Studies at the DNA and rRNA level support the subdivision of the species into groups I-IV. Most outbreaks of human botulism are caused by group I (proteolytic) or II (non-proteolytic) C. botulinum. Group III organisms mainly cause diseases in animals. Group IV C. botulinum has not been shown to cause human or animal disease.

Botulinum toxin

Neurotoxin production is the unifying feature of the species. Eight types of toxins have been identified (including the recently described type H) that are allocated a letter (A-H).[7] All toxins are rapidly destroyed at 100°C, but they are resistant to degradation by enzymes found in the gastrointestinal tract. This allows for ingested toxin to be absorbed from the intestines into the bloodstream.[3]

Most strains produce one type of neurotoxin, 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.[10] 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 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, indicating that the C. botulinum acquired the toxin genes quite far in the evolutionary past.

Botulinum toxin types

Only botulinum toxin types A, B, E, F, and H cause disease in humans. Types A, B, and E are associated with foodborne illness, with type E specifically associated with fish products. Type C produces limberneck in birds and type D causes botulism in other mammals. No disease is associated with type G.[11] 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.[12]

A few strains from organisms genetically identified as other Clostridium species have caused human botulism: C. butyricum has produced type E toxin[13] and C. baratii had produced type F toxin.[14][15] 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.

An eighth toxin, type H, was discovered by researchers at the California Department of Public Health in 2013. With a lethal dose of 2 ng by injection or 13 ng by inhalation, it was deemed the most toxic substance on Earth.[7]

Phenotypic groups of Clostridium botulinum

Properties

Group I

Group II

Group III

Group IV

Toxin Types

A, B, F B, E, F C, D G

Proteolysis

+ - weak -

Saccharolysis

- + - -

Disease host

human human animal -

Toxin gene

chromosome/plasmid chromosome/plasmid bacteriophage plasmid

Close relatives

C. sporogenes, C. putrificum C. butyricum, C. beijerinickii C. haemolyticum, C. novyi type A C. subterminale, C. haemolyticum

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 commercial kits that use a chemical reaction to replace O2 with CO2. C. botulinum 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.[16]

Taxonomy history

C. botulinum was first recognized and isolated in 1895 by Emile van Ermengem from home-cured ham implicated in a botulism outbreak.[17] 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)[18] However, isolates from subsequent outbreaks were always found to be anaerobic spore formers, so Ida A. Bengtson proposed that the organism be placed into the genus Clostridium, as the Bacillus genus was restricted to aerobic spore-forming rods.[19]

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. This has led to the reclassification of C. botulinum type G strains as a new species, C. argentinense.[20]

Group I C. botulinum strains that do not produce a botulin toxin are referred to as C. sporogenes.[21]

The complete genome of C. botulinum has been sequenced at Sanger.[22]

C. botulinum in different geographical locations

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.

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.[23] The type-B organisms were of the proteolytic type I. Sediments from the Great Lakes region were surveyed after outbreaks of botulism among commercially reared fish, and only type E spores were detected.[24][25][26] In a survey, type-A strains were isolated from soils that were neutral to alkaline (average pH 7.5), while type-B strains were isolated from slightly acidic soils (average pH 6.25).

Europe

C. botulinum type E is prevalent in aquatic sediments in Norway and Sweden,[27] Denmark,[28] the Netherlands, the Baltic coast of Poland, and Russia.[23] The type-E C. botulinum was suggested to be a true 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.

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 proteolytic C. botulinum types A or B.[29]

Australia

C. botulinum type A was found to be present in soil samples from mountain areas of Victoria.[30] Type-B organisms were detected in marine mud from Tasmania.[31] Type-A C. botulinum has been found in Sydney suburbs and types A and B were isolated from urban areas. In a well-defined area of the Darling-Downs region of Queensland, a study showed the prevalence and persistence of C. botulinum type B after many cases of botulism in horses.

Other

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,[32] and quantitative PCR can detect the toxin genes in the organism.[12]

C. botulinum is also 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.

Botulin 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 (Template:LD50 of 1 ng/kg,[33] assuming an average person weighs ~75 kg); 1 kilogram of it would be enough to kill the entire human population. For comparative purposes, a quarter of a typical grain of sand's weight (350 ng) of botulinum toxin would constitute a lethal dose for humans.

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.

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; 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.


Gallery

References

  1. ↑ 1.0 1.1 1.2 Peck, MW (2009). "Biology and genomic analysis of Clostridium botulinum". Advances in microbial physiology. Advances in Microbial Physiology. 55: 183–265, 320. doi:10.1016/s0065-2911(09)05503-9. ISBN 9780123747907. PMID 19573697.
  2. ↑ 2.0 2.1 Lindström, M; Korkeala, H (Apr 2006). "Laboratory diagnostics of botulism". Clinical Microbiology Reviews. 19 (2): 298–314. doi:10.1128/cmr.19.2.298-314.2006. PMC 1471988. PMID 16614251.
  3. ↑ 3.0 3.1 (2010). Chapter 29. Clostridium, Peptostreptococcus, Bacteroides, and Other Anaerobes. In Ryan K.J., Ray C (Eds), Sherris Medical Microbiology, 5th ed. ISBN 978-0071604024
  4. ↑ Doyle, Michael P. (2007). Food Microbiology: Fundamentals and Frontiers. ASM Press. ISBN 1-55581-208-2.
  5. ↑ Peck, MW; Stringer, SC; Carter, AT. (2011). "Clostridium botulinum in the post-genomic era". Food Microbiol. 28 (2): 183–91. doi:10.1016/j.fm.2010.03.005. PMID 21315972.
  6. ↑ Shukla, HD; Sharma, SK. (2005). "Clostridium botulinum: a bug with beauty and weapon". Crit Rev Microbiol. 31 (1): 11–8. doi:10.1080/10408410590912952. PMID 15839401.
  7. ↑ 7.0 7.1 7.2 MacKenzie, Debora (14 October 2013). "New botox super-toxin has its details censored". NewScientist. Retrieved 15 October 2013.
  8. ↑ L. V. Holdeman, J. B. Brooks. 1970. Variation among strains of Clostridium botulinum and related clostridia. Protocols of the first U.S-Japan conference on Toxic Microorganisms. pp. 278–286
  9. ↑ L. D. S. Smith, G. Hobbs. 1974. Genus III Clostridium Prazmowski 1880, 23. In R. E. Buchanan, N. E. gibbons (eds.), Bergey’s Manual of Determinative Bacteriology, 8th ed. William & Wilkins, Baltimore. pp. 551–572. ISBN 978-0683006032
  10. ↑ Hatheway, C. L.; McCroskey, L. M. (1987). "Examination of faeces for diagnosis of infant botulism in 336 patients". J. Clin. Microbiol. 25 (12): 2334–2338. PMC 269483. PMID 3323228.
  11. ↑ (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 978-0071790314
  12. ↑ 12.0 12.1 Satterfield, B. A.; Stewart, A. F.; Lew, C. S.; Pickett, D. O.; Cohen, M. N.; Moore, E. A.; Luedtke, P. F.; O'Neill, K. L.; Robison, R. A.; et al. (2010). "A quadruplex real-time PCR assay for rapid detection and differentiation of the Clostridium botulinum toxin genes A, B, E and F". J Med Microbiol. 59 (Pt 1): 55–64. doi:10.1099/jmm.0.012567-0. PMID 19779029.
  13. ↑ Aureli, P.; Fenicia, L.; Pasolini, B.; Gianfrancesche, M.; Mccroskey, J. M.; Hatheway, C. L. (1986). "Two cases of type E infant botulism caused by neurotoxigenic Clostridium botulinum in Italy". J. Infect. Dis. 154 (2): 207–211. doi:10.1093/infdis/154.2.207. PMID 3722863.
  14. ↑ Hall, J. D.; McCroskey, L. M.; Pincomb, B. J.; Hatheway, C. L. (1985). "Isolation of an organism resembling Clostridium baratii which produces a type F botulinal toxin from an infant with botulism". J. Clin. Microbiol. 21 (4): 654–655. PMC 271744. PMID 3988908.
  15. ↑ Notermans, S.; Havellar, A. H. (1980). "Removal and inactivation of botulinum toxin during production of drinking water from surface water". Antonie van Leeuwenhoek. 46 (5): 511–514. doi:10.1007/BF00395840.
  16. ↑ . (2005). Brock Biology of Microorganisms (11th ed.). Prentice Hall. ISBN 0-13-144329-1.
  17. ↑ E. van Ergmengem. 1897. Über einen neuen anaeroben Bacillus und seine Beziehungen Zum Botulismus. Zentralbl. Hyg. Infektionskr. 26:1–8.
  18. ↑ Frank J. Erbguth. Historical notes on botulism, Clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin. Movement Disorders. Volume 19, Issue S8, pages S2-S6, March 2004.
  19. ↑ I. A. Bengston. 1924. Studies on organisms concerned as causative factors in botulism. Hyg. Lab. Bull. 136:101
  20. ↑ J. C. Suen, C. L. Hatheway, A. G. Steigerwalt, D. J. Brenner. 1988, Clostridium argentinense sp.nov.: a genetically homogeneous group composed of all strains of Clostridium botulinum type G and some nontoxigenic strains previously identified as Clostridium subterminale or Clostridium hastiforme. Int. J. Sys. Bacteriol. 38:375–381.
  21. ↑ Judicial Commission of the International Committee on Systematic Bacteriology (1999) Rejection of Clostridium putrificum and conservation of Clostridium botulinum and Clostridium sporogenes Opinion 69. International Journal of Systematic Bacteriology. 49:339.
  22. ↑ http://www.sanger.ac.uk/Projects/C_botulinum/
  23. ↑ 23.0 23.1 A. H. W. Hauschild. 1989. Clostridium botulinum. In M. P. Doyle (ed.), Food-borne Bacterial Pathogens. Marcel Dekker, New York. Pp. 111–189
  24. ↑ Bott, T. L.; Johnson, J.; Foster, E. M.; Sugiyama, H. (1968). "Possible origin of the fish incidences of Clostridium botulinum type E in an inland bay (Green Bay of Lake Michigan)". J. Bacteriol. 95: 1542.
  25. ↑ M. W. Eklund, M. E. Peterson, F. T. Poysky, L. W. Peck, J. F. Conrad. 1982. Botulism in juvenile Coho salmon (Onocorhynchus kisutch) in the United States. Aquaculture 27:1–11
  26. ↑ M. W. Eklund, F. T. Poysky M. E. Peterson, L. W. Peck, Brunson. 1984. Type E botulism in salmonids and conditions contributing to outbreaks. Aquaculture 41:293–309.
  27. ↑ A. Johannsen. 1963. Clostridium botulinum in Sweden and the adjacent waters. J. Appl. Bacteriol. 26:43–47.
  28. ↑ Huss, H. H. (1980). "Distribution of Clostridium botulinum". Appl. Environ. Microbiol. 39 (4): 764–769. PMC 291416. PMID 6990867.
  29. ↑ Creti, R.; Fenicia, J.; Aureli, P. (1990). "Occurrence of Clostridium botulinum in the soil of the vicinity of Rome". Curr. Microbiol. 20 (5): 317. doi:10.1007/bf02091912.
  30. ↑ Eales, C. E.; Gillespie, J. M. (1947). "the isolation of Clostridium botulinum type A from Victorian soils. Aust. J". Sci. 10: 20–21.
  31. ↑ Ohye, W. J. Scott (1957). "Studies in the physiology of Clostridium botulinum type E. Aust. L. Biol". Sci. 10: 85–94.
  32. ↑ Shashi K. Sharma, Joseph. L. Ferreira, Brian S. Eblen and Richard C. Whitingand. 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. Appl. Environ. Microbiol. February 2006 vol. 72 no. 2 1231-1238. doi:10.1128/AEM.72.2.1231-1238.2006
  33. ↑ Fleming, Diane O. "Biological Safety: principles and practices". ASM Press. 2000: 267.
  34. ↑ 34.0 34.1 34.2 "Public Health Image Library (PHIL)".

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