Editing Clostridium perfringens (section)

=== Major toxins ===
There are five major toxins produced by ''Clostridium perfringens.'' Alpha, beta, epsilon and enterotoxin are toxins that increase a cells permeability which causes an ion imbalance while iota toxins destroy the cell's actin cytoskeleton.<ref name="Stiles-20132">{{Cite journal |last1=Stiles |first1=Bradley G. |last2=Barth |first2=Gillian |last3=Barth |first3=Holger |last4=Popoff |first4=Michel R. |date=2013-11-12 |title=Clostridium perfringens Epsilon Toxin: A Malevolent Molecule for Animals and Man? |journal=Toxins |volume=5 |issue=11 |pages=2138–2160 |doi=10.3390/toxins5112138 |issn=2072-6651 |pmc=3847718 |pmid=24284826 |doi-access=free}}</ref> On the basis of which major, "typing" toxins are produced, ''C. perfringens'' can be classified into seven "toxinotypes", A, B, C, D, E, F and G:<ref name="pmid351488122">{{cite journal |vauthors=Johnston MD, Whiteside TE, Allen ME, Kurtz DM |date=February 2022 |title=Toxigenic Profile of Clostridium perfringens Strains Isolated from Natural Ingredient Laboratory Animal Diets |url= |journal=Comparative Medicine |volume=72 |issue=1 |pages=50–58 |doi=10.30802/AALAS-CM-22-000013 |pmc=8915413 |pmid=35148812}}</ref>
{| class="wikitable"
|+Toxinotypes of ''C. perfringens''<ref name="pmid351488122" />{{rp|at=fig.1}}<ref>{{Cite journal |last1=Rood |first1=Julian I. |last2=Adams |first2=Vicki |last3=Lacey |first3=Jake |last4=Lyras |first4=Dena |last5=McClane |first5=Bruce A. |last6=Melville |first6=Stephen B. |last7=Moore |first7=Robert J. |last8=Popoff |first8=Michel R. |last9=Sarker |first9=Mahfuzur R. |last10=Songer |first10=J. Glenn |last11=Uzal |first11=Francisco A. |last12=Van Immerseel |first12=Filip |date=2018-10-01 |title=Expansion of the Clostridium perfringens toxin-based typing scheme |journal=Anaerobe |volume=53 |pages=5–10 |doi=10.1016/j.anaerobe.2018.04.011 |issn=1075-9964 |pmc=6195859 |pmid=29866424 |doi-access=free}}</ref>
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!Alpha
!Beta
!Epsilon
!Iota
!Enterotoxin
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==== Alpha toxin ====
Alpha toxin (CPA) is a zinc-containing phospholipase C, composed of two structural domains, which destroy a cell's membrane. Alpha toxins are produced by all five types of ''C. perfringens.'' This toxin is linked to [[gas gangrene]] of humans and animals. Most cases of gas gangrene has been related to a deep wound being contaminated by soil that harbors ''C. perfringens''.<ref name="Stiles-20132" /><ref>{{Cite journal |last1=Li |first1=Ming |last2=Li |first2=Ning |date=2021-06-16 |title=Clostridium perfringens bloodstream infection secondary to acute pancreatitis: A case report |journal=World Journal of Clinical Cases |volume=9 |issue=17 |pages=4357–4364 |doi=10.12998/wjcc.v9.i17.4357 |issn=2307-8960 |pmc=8173429 |pmid=34141801 |doi-access=free}}</ref>

==== Beta toxin ====
Beta toxins (CPB) are a protein that causes hemorrhagic [[Clostridial necrotizing enteritis|necrotizing enteritis]] and [[Enterotoxemia|enterotoxaemia]] in both animals (type B) and humans (type C) which leads to the infected individual's feces becoming bloody and their intestines necrotizing.<ref name="Stiles-20132" /> [[Protease|Proteolytic enzymes]], such as trypsin, can break down CPB, making them ineffective. Therefore, the presence of trypsin inhibitors in colostrum makes CPB especially deadly for mammal offspring.<ref>{{Cite journal |last1=Garcia |first1=J.P. |last2=Beingesser |first2=J. |last3=Fisher |first3=D.J. |last4=Sayeed |first4=S. |last5=McClane |first5=B.A. |last6=Posthaus |first6=H. |last7=Uzal |first7=F.A. |date=4 January 2012 |title=The effect of Clostridium perfringens type C strain CN3685 and its isogenic beta toxin null mutant in goats |journal=Veterinary Microbiology |language=en |volume=157 |issue=3–4 |pages=412–419 |doi=10.1016/j.vetmic.2012.01.005 |pmc=3348370 |pmid=22296994}}</ref>

==== Epsilon toxin ====
Epsilon toxin (ETX) is a protein produced by type B and type D strains of ''C. perfringens.'' This toxin is currently ranked the third most potent bacterial toxin known.<ref>{{Cite journal |last1=Alves |first1=Guilherme Guerra |last2=Machado de Ávila |first2=Ricardo Andrez |last3=Chávez-Olórtegui |first3=Carlos Delfin |last4=Lobato |first4=Francisco Carlos Faria |date=2014-12-01 |title=Clostridium perfringens epsilon toxin: The third most potent bacterial toxin known |url=https://www.sciencedirect.com/science/article/pii/S1075996414001309 |journal=Anaerobe |volume=30 |pages=102–107 |doi=10.1016/j.anaerobe.2014.08.016 |issn=1075-9964 |pmid=25234332|url-access=subscription }}</ref> ETX causes [[Enterotoxemia|enterotoxaemia]] in mainly goats and sheep, but cattle are sometime susceptible to it as well. An experiment using mice found that ETX had an LD50 of 50-110&nbsp;ng/kg.<ref>{{Cite journal |last1=Xin |first1=Wenwen |last2=Wang |first2=Jinglin |date=2019-09-01 |title=Clostridium perfringens epsilon toxin: Toxic effects and mechanisms of action |journal=Biosafety and Health |volume=1 |issue=2 |pages=71–75 |doi=10.1016/j.bsheal.2019.09.004 |issn=2590-0536 |s2cid=208690896 |doi-access=free}}</ref> The excessive production of ETX increases the permeability of the intestines. This causes severe edema in organs such as the brain and kidneys.<ref>{{Cite journal |last1=Geng |first1=Zhijun |last2=Kang |first2=Lin |last3=Huang |first3=Jing |last4=Gao |first4=Shan |last5=Wang |first5=Jing |last6=Yuan |first6=Yuan |last7=Li |first7=Yanwei |last8=Wang |first8=Jinglin |last9=Xin |first9=Wenwen |date=2021-07-30 |title=Epsilon toxin from Clostridium perfringens induces toxic effects on skin tissues and HaCaT and human epidermal keratinocytes |journal=Toxicon |volume=198 |pages=102–110 |bibcode=2021Txcn..198..102G |doi=10.1016/j.toxicon.2021.05.002 |issn=0041-0101 |pmid=33965432 |s2cid=234343237 |doi-access=free}}</ref>

The very low LD50 of ETX has led to concern that it may be used as a bioweapon. It appeared on the [[select agent]] lists of the US CDC and USDA, until it was removed in 2012. There are no human vaccines for this toxin, but effective vaccines for animals exist.<ref name="MEDCOE2">{{cite book |last1=Stiles |first1=Bradley G. |url=https://medcoe.army.mil/borden-tb-medical-aspects-bio-war |title=Medical Aspects of Biological Warfare |last2=Barth |first2=Gillian |last3=Popoff |first3=Michel R. P |date=2018 |publisher=Health Readiness Center of Excellence (US Army) |isbn=9780160941597 |edition=2 |chapter=Clostridium Perfringens Epsilon Toxin}}</ref>

==== Iota toxin ====
Iota toxin (ITX) is a protein produced by type E strains of ''C. perfringens.'' Iota toxins are made up of two, unlinked proteins that form a multimeric complex on cells. Iota toxins prevent the formation of filamentous actin. This causes the destruction of the cells cytoskeleton which in turn leads to the death of the cell as it can no longer maintain homeostasis.<ref>{{Cite journal |last1=Sakurai |first1=Jun |last2=Nagahama |first2=Masahiro |last3=Oda |first3=Masataka |last4=Tsuge |first4=Hideaki |last5=Kobayashi |first5=Keiko |date=2009-12-23 |title=Clostridium perfringens Iota-Toxin: Structure and Function |journal=Toxins |volume=1 |issue=2 |pages=208–228 |doi=10.3390/toxins1020208 |issn=2072-6651 |pmc=3202787 |pmid=22069542 |doi-access=free}}</ref>

==== Enterotoxin ====
This toxin (CPE) causes food poisoning. It alters intracellular claudin tight junctions in gut epithelial cells. This pore-forming toxin also can bind to human ileal and colonic epithelium in vitro and necrotize it. Through the caspase-3 pathway, this toxin can cause apoptosis of affected cells. This toxin is linked to type F strains, but has also been found to be produced by certain types of C, D, and E strains.<ref>{{Cite journal |last1=Kiu |first1=Raymond |last2=Hall |first2=Lindsay J. |date=2018-12-01 |title=An update on the human and animal enteric pathogen Clostridium perfringens |journal=Emerging Microbes & Infections |language=en |volume=7 |issue=1 |page=141 |doi=10.1038/s41426-018-0144-8 |issn=2222-1751 |pmc=6079034 |pmid=30082713 |doi-access=free}}</ref>