Editing Clostridium perfringens

{{Short description|Species of bacterium}}
{{Speciesbox
| image = Clostridium_perfringens.jpg
| image_caption = Photomicrograph of Gram-positive ''Clostridium perfringens'' bacilli
| genus = Clostridium
| species = perfringens
| authority = Veillon & Zuber 1898<br />Hauduroy ''et al.'' 1937
}}

'''''Clostridium perfringens''''' (formerly known as ''C. [[William H. Welch|welchii]]'', or ''Bacillus welchii'') is a [[Gram-positive]], bacillus (rod-shaped), [[anaerobic bacterium|anaerobic]], [[Endospore|spore-forming]] [[pathogenic bacterium]] of the genus ''[[Clostridium]]''.<ref>{{cite book|last1=Ryan|first1=Kenneth J.|last2=Ray|first2=C. George|title=Sherris Medical Microbiology : an Introduction to Infectious Diseases|date=2004|publisher=McGraw-Hill|location=New York|isbn=978-0-8385-8529-0|page=310|edition=4th}}</ref><ref>{{cite journal |last1=Kiu |first1=R |last2=Hall |first2=L. J. |title=An update on the human and animal enteric pathogen ''Clostridium perfringens'' |journal=Emerging Microbes & Infections |volume=7 |issue=141 |pages=141|pmc=6079034|year=2018 |pmid=30082713 |doi=10.1038/s41426-018-0144-8 }}</ref> ''C. perfringens'' is ever-present in nature and can be found as a normal component of decaying vegetation, [[Pelagic sediment|marine sediment]], the [[Gut flora|intestinal tract of humans]] and other [[vertebrate]]s, [[insect]]s, and [[soil]]. It has the shortest reported [[generation time]] of any organism at 6.3 minutes in [[thioglycolate broth|thioglycolate]] medium.<ref name=bionumbers>{{cite web|title=BioNumber Details Page|work=BioNumbers|url=http://bionumbers.hms.harvard.edu//bionumber.aspx?id=105474&ver=1}}</ref>

''Clostridium perfringens'' is one of the most common causes of [[food poisoning]] in the United States, alongside [[norovirus]], ''[[Salmonella]]'', ''[[Campylobacter]]'', and ''[[Staphylococcus aureus]]''.<ref>{{cite web|title=Foodborne Illnesses and Germs|url=https://www.cdc.gov/foodsafety/foodborne-germs.html|website=Centers for Disease Control and Prevention (CDC)|access-date=18 February 2018|date=2018-02-16}}</ref> However, it can sometimes be ingested and cause no harm.<ref name=Jucket2008>{{cite journal |pmid=18646681 |year=2008 |last1=Juckett |first1=G |last2=Bardwell |first2=G |last3=McClane |first3=B |last4=Brown |first4=S |title=Microbiology of salt rising bread |volume=104 |issue=4 |pages=26–7 |journal=The West Virginia Medical Journal}}</ref>

Infections induced by ''C. perfringens'' are associated with tissue [[necrosis]], [[bacteremia]], emphysematous [[cholecystitis]], and [[gas gangrene]], which is also known as clostridial [[myonecrosis]].<ref>{{Cite journal |last1=Hendrix |first1=Nancy |last2=Mackeen |first2=A. |last3=Weiner |first3=Stuart |date=2011-01-24 |title=Clostridium perfringens Sepsis and Fetal Demise after Genetic Amniocentesis |journal=American Journal of Perinatology Reports |language=en |volume=1 |issue=1 |pages=025–028 |doi=10.1055/s-0030-1271221 |pmid=23705080 |pmc=3653538 |issn=2157-6998}}</ref> The specific name, ''perfringens,'' is derived from the [[Latin]] {{Lang|la|per}} (meaning "through") and {{Lang|la|frango}} ("burst"), referring to the disruption of tissue that occurs during gas gangrene.<ref>{{cite book |title=Lexicon Orthopaedic Etymology |date=1999 |publisher=CRC Press |isbn=9789057025976 |page=128 |url=https://books.google.com/books?id=fstFQVnw8-wC |language=en}}</ref> Gas gangrene is caused by alpha toxin, or [[Clostridium perfringens alpha toxin|α-toxin]], that embeds itself into the plasma membrane of cells and disrupts normal cellular function by altering membrane structure.<ref name=":32">{{Cite journal |last1=Hendrix |first1=Nancy |last2=Mackeen |first2=A. |last3=Weiner |first3=Stuart |date=2011-01-24 |title=Clostridium perfringens Sepsis and Fetal Demise after Genetic Amniocentesis |journal=American Journal of Perinatology Reports |language=en |volume=1 |issue=1 |pages=025–028 |doi=10.1055/s-0030-1271221 |issn=2157-6998 |pmc=3653538 |pmid=23705080}}</ref> Research suggests that ''C. perfringens'' is capable of engaging in polymicrobial [[anaerobic infection]]s.<ref name=":4">{{Cite journal |last1=Takehara |first1=Masaya |last2=Takagishi |first2=Teruhisa |last3=Seike |first3=Soshi |last4=Ohtani |first4=Kaori |last5=Kobayashi |first5=Keiko |last6=Miyamoto |first6=Kazuaki |last7=Shimizu |first7=Tohru |last8=Nagahama |first8=Masahiro |date=2016-06-16 |title=Clostridium perfringens α-Toxin Impairs Innate Immunity via Inhibition of Neutrophil Differentiation |journal=Scientific Reports |language=en |volume=6 |issue=1 |page=28192 |doi=10.1038/srep28192 |issn=2045-2322 |pmc=4910053 |pmid=27306065|bibcode=2016NatSR...628192T }}</ref> It is commonly encountered in [[infection]]s as a component of the normal [[flora (microbiology)|flora]]. In this case, its role in disease is minor.<ref>{{Cite journal |last1=Grenda |first1=Tomasz |last2=Jarosz |first2=Aleksandra |last3=Sapała |first3=Magdalena |last4=Grenda |first4=Anna |last5=Patyra |first5=Ewelina |last6=Kwiatek |first6=Krzysztof |date=2023-05-26 |title=Clostridium perfringens—Opportunistic Foodborne Pathogen, Its Diversity and Epidemiological Significance |journal=Pathogens |language=en |volume=12 |issue=6 |pages=768 |doi=10.3390/pathogens12060768 |doi-access=free |issn=2076-0817 |pmc=10304509 |pmid=37375458}}</ref>

''C. perfringens'' toxins are a result of horizontal gene transfer of a neighboring cell's plasmids.<ref name="Gulliver-2023" /> Shifts in genomic make-up are common for this species of bacterium and contribute to novel pathogenesis.<ref name="Elnar-2021" /> Major toxins are expressed differently in certain populations of ''C. perfringens;'' these populations are organized into strains based on their expressed toxins.<ref name="Revitt-Mills-20152">{{Cite journal |last1=Revitt-Mills |first1=Sarah A |last2=Rood |first2=Julian I |last3=Adams |first3=Vicki |date=2015 |title=Clostridium perfringens extracellular toxins and enzymes: 20 and counting |url=http://microbiology.publish.csiro.au/?paper=MA15039 |journal=Microbiology Australia |language=en |volume=36 |issue=3 |pages=114 |doi=10.1071/MA15039 |doi-broken-date=3 March 2025 |issn=1324-4272 |doi-access=free}}</ref> This especially impacts the food industry, as controlling this microbe is important for preventing foodborne illness.<ref name="Elnar-2021" /> Novel findings in ''C. perfringens'' hyper-motility, which was provisionally thought as non-motile, have been discovered as well.<ref name="Wambui-2021">{{Cite journal |last1=Wambui |first1=Joseph |last2=Cernela |first2=Nicole |last3=Stevens |first3=Marc J. A. |last4=Stephan |first4=Roger |date=2021-09-13 |title=Whole Genome Sequence-Based Identification of Clostridium estertheticum Complex Strains Supports the Need for Taxonomic Reclassification Within the Species Clostridium estertheticum |journal=Frontiers in Microbiology |volume=12 |doi=10.3389/fmicb.2021.727022 |issn=1664-302X |pmc=8473909 |pmid=34589074 |doi-access=free}}</ref> Findings in metabolic processes reveal more information concerning ''C. perfringens'' pathogenic nature.<ref name="Ohtani-2016" />

== Genome ==
''Clostridium perfringens'' has a stable [[GC-content|G+C content]] around 27 to 28 percent and average [[genome]] size of 3.5 Mb.<ref name="Kiu-2017" /> Genomes of 56 ''C. perfringens'' strains have since been made available on the [[NCBI]] genomes database for the scientific research community. [[Genomics|Genomic]] research has revealed surprisingly high diversity in ''C. perfringens'' [[Pan-genome|pangenome]], with only 12.6 percent core genes, identified as the most divergent Gram-positive [[bacteria]] reported.<ref name="Kiu-2017" /> Nevertheless, [[16S rRNA]] regions in between ''C. perfringens'' strains are found to be highly conserved ([[sequence identity]] >99.1%).<ref name="Kiu-2017">{{Cite journal|last1=Kiu|first1=Raymond|last2=Caim|first2=Shabhonam|last3=Alexander|first3=Sarah|last4=Pachori|first4=Purnima|last5=Hall|first5=Lindsay J.|date=2017|title=Probing Genomic Aspects of the Multi-Host Pathogen Clostridium perfringens Reveals Significant Pangenome Diversity, and a Diverse Array of Virulence Factors|journal=Frontiers in Microbiology|language=en|volume=8|pages=2485|pmc=5733095|pmid=29312194|doi=10.3389/fmicb.2017.02485|doi-access=free}}</ref>

The ''Clostridium perfringens'' enterotoxin (CPE)–producing strain has been identified to be a small portion of the overall ''C. perfringens'' population (~1-5%) through genomic testing.<ref name="Miyamoto-2012">{{Cite journal |last1=Miyamoto |first1=Kazuaki |last2=Li |first2=Jihong |last3=McClane |first3=Bruce A. |date=2012 |title=Enterotoxigenic Clostridium perfringens: Detection and Identification |journal=Microbes and Environments |language=en |volume=27 |issue=4 |pages=343–349 |doi=10.1264/jsme2.ME12002 |pmid=22504431 |pmc=4103540 |s2cid=7743606 |issn=1342-6311|doi-access=free }}</ref> Advances in genetic information surrounding strain A CPE ''C. perfringens'' has allowed techniques such as microbial source tracking (MST) to identify food contamination sources.<ref name="Miyamoto-2012" /> The CPE gene has been found within chromosomal DNA as well as plasmid DNA. Plasmid DNA has been shown to play and integral role in cell pathogenesis and encodes for major toxins, including CPE.<ref name="Gulliver-2023">{{Cite journal |last1=Gulliver |first1=Emily L. |last2=Adams |first2=Vicki |last3=Marcelino |first3=Vanessa Rossetto |last4=Gould |first4=Jodee |last5=Rutten |first5=Emily L. |last6=Powell |first6=David R. |last7=Young |first7=Remy B. |last8=D’Adamo |first8=Gemma L. |last9=Hemphill |first9=Jamia |last10=Solari |first10=Sean M. |last11=Revitt-Mills |first11=Sarah A. |last12=Munn |first12=Samantha |last13=Jirapanjawat |first13=Thanavit |last14=Greening |first14=Chris |last15=Boer |first15=Jennifer C. |date=2023-04-20 |title=Extensive genome analysis identifies novel plasmid families in Clostridium perfringens |journal=Microbial Genomics |language=en |volume=9 |issue=4 |doi=10.1099/mgen.0.000995 |pmid=37079454 |pmc=10210947 |s2cid=258238878 |issn=2057-5858|doi-access=free }}</ref>

''C. perfringens'' has been shown to carry plasmid-containing genes for [[antibiotic resistance]]. The pCW3 plasmid is the primary conjugation plasmid responsible for creating antibiotic resistance in ''C. perfringens''. Furthermore, the pCW3 plasmid also encodes for multiple toxins found in pathogenic strains of ''C. perfringens''.<ref>{{Cite journal |last1=Adams |first1=Vicki |last2=Han |first2=Xiaoyan |last3=Lyras |first3=Dena |last4=Rood |first4=Julian I. |date=September 2018 |title=Antibiotic resistance plasmids and mobile genetic elements of Clostridium perfringens |url=https://linkinghub.elsevier.com/retrieve/pii/S0147619X18300726 |journal=Plasmid |language=en |volume=99 |pages=32–39 |doi=10.1016/j.plasmid.2018.07.002|pmid=30055188 |s2cid=51866356 |url-access=subscription }}</ref> Antibiotic resistance genes observed thus far include [[tetracycline]] resistance, efflux protein, and [[aminoglycoside]] resistance.<ref>{{Cite journal |last1=Kiu |first1=Raymond |last2=Caim |first2=Shabhonam |last3=Alexander |first3=Sarah |last4=Pachori |first4=Purnima |last5=Hall |first5=Lindsay J. |date=2017-12-12 |title=Probing Genomic Aspects of the Multi-Host Pathogen Clostridium perfringens Reveals Significant Pangenome Diversity, and a Diverse Array of Virulence Factors |journal=Frontiers in Microbiology |volume=8 |page=2485 |doi=10.3389/fmicb.2017.02485 |issn=1664-302X|doi-access=free |pmid=29312194 |pmc=5733095 }}</ref>

Within industrial contexts, such as [[food production]], sequencing genomes for pathogenic strains of ''C. perfringens'' has become an expanding field of research. Poultry production is impacted directly from this trend as antibiotic-resistant strains of ''C. perfringens'' are becoming more common.<ref name="Elnar-2021">{{Cite journal |last1=Elnar |first1=Arxel G. |last2=Kim |first2=Geun-Bae |date=2021-11-30 |title=Complete genome sequence of Clostridium perfringens B20, a bacteriocin-producing pathogen |journal=Journal of Animal Science and Technology |language=en |volume=63 |issue=6 |pages=1468–1472 |doi=10.5187/jast.2021.e113 |issn=2672-0191|doi-access=free |pmid=34957460 |pmc=8672250 }}</ref> By performing a meta-genome analysis, researches are capable to identify novel strains of pathogenic bacterium, such as ''C. perfringens'' B20.<ref name="Elnar-2021" />

== Motility ==
''Clostridium perfringens'' is provisionally identified as non-motile. They lack flagella; however, recent research suggests gliding as a form of motility.<ref name=":0" /><ref name=":1">{{Cite journal |last1=Valeriani |first1=Renzo G. |last2=Beard |first2=LaMonta L. |last3=Moller |first3=Abraham |last4=Ohtani |first4=Kaori |last5=Vidal |first5=Jorge E. |date=2020-12-01 |title=Gas gangrene-associated gliding motility is regulated by the Clostridium perfringens CpAL/VirSR system |url=https://www.sciencedirect.com/science/article/pii/S1075996420301438 |journal=Anaerobe |volume=66 |pages=102287 |doi=10.1016/j.anaerobe.2020.102287 |pmid=33130105 |issn=1075-9964|url-access=subscription }}</ref>

=== Hyper-motile variations ===
[[File:21913 lores.jpg|thumb|248x248px|This illustration depicts a three-dimensional (3D), computer-generated image of a cluster of barrel-shaped, ''Clostridium perfringens'' bacteria. The artistic recreation was based upon scanning electron microscopic (SEM) imagery.]]
In agar plate cultures bacteria with hypermotile variations like SM101 frequently appear around the borders of the colonies. They create long thin filaments that enable them to move quickly, much like bacteria with flagella, according to video imaging of their gliding motion. The causes of the hypermotile phenotype and its immediate descendants were found using genome sequencing. The hypermotile offspring of strains SM101 and SM102, SM124 and SM127, respectively, had 10 and 6 nucleotide polymorphisms (SNPs) in comparison to their parent strains. The hypermotile strains have the common trait of gene mutations related to cell division.<ref name=":0">{{Cite journal |last1=Liu |first1=Hualan |last2=McCord |first2=Kristin D. |last3=Howarth |first3=Jonathon |last4=Popham |first4=David L. |last5=Jensen |first5=Roderick V. |last6=Melville |first6=Stephen B. |date=July 2014 |title=Hypermotility in Clostridium perfringens Strain SM101 Is Due to Spontaneous Mutations in Genes Linked to Cell Division |journal=Journal of Bacteriology |volume=196 |issue=13 |pages=2405–2412 |doi=10.1128/JB.01614-14 |issn=0021-9193 |pmc=4054169 |pmid=24748614}}</ref>

=== Regulation of gliding motility: The CpAL/VirSR system ===
Some strains of ''C. perfringens'' cause various diseases like gas gangrene and myonecrosis. Toxins produced that are required for myonecrosis is regulated by the ''C. perfringens'' Agr-like (CpAl) system through the VirSR two-component system. The CpAL/VirSR system is a quorum sensing system encoded by other pathogenic clostridia. Myonecrosis starts at the infection site and involves bacteria migrating deeper via gliding motility. Researchers investigated if the CpAL/VirSR system regulates gliding motility. The study demonstrated that the CpAL/VirSR regulates ''C. perfringens'' gliding motility. Additionally, the study suggests that gliding bacteria in myonecrosis have&nbsp;increased transcription of toxin genes.<ref name=":1" />

== Transformation ==
{{main|Transformation (genetics)}}
There are two methods of [[Genetic engineering|genetic manipulation]] via experimentation that have been shown to cause genetic transformation in ''C. perfringens''.

=== Protoplast transformation ===
The first report of transformation in ''C. perfringens'' involved [[polyethylene]] [[Glycol|glycol-mediated transformation]] of [[protoplast]]s. The transformation procedure involved the addition of the plasmid DNA to the protoplasts in the presence of high concentrations of [[polyethylene glycol]]. During the first protoplast transformation experiment, L-phase variants of ''C. perfringens'' were generated by [[penicillin]] treatment in the presence 0.4m sucrose. After the transformation procedure was completed, all of the transformed cells were still in the form of L-phase variants. Reversion to vegetative cells was not obtained, but it was observed that autoplasts (protoplasts derived from [[Autolysis (biology)|autolysis]]) were able to be regenerated to produce rods with cell walls and could be transformed with ''C. perfringens'' plasmid DNA.<ref>{{Cite journal |last1=Rood |first1=J I |last2=Cole |first2=S T |date=December 1991 |title=Molecular genetics and pathogenesis of Clostridium perfringens |journal=Microbiological Reviews |language=en |volume=55 |issue=4 |pages=621–648 |doi=10.1128/mr.55.4.621-648.1991 |issn=0146-0749 |pmc=372840 |pmid=1779929}}</ref>

=== Electroporation ===
[[Electroporation]] involves the application of a high-voltage electric field to vegetative bacteria cells for a very short period. This technique resulted in major advances in genetic transformation of ''C. perfringens'', due to the bacteria often displaying itself as a vegetative cell or as dormant spores in food.<ref>{{Cite journal |last1=Golden |first1=Neal J. |last2=Crouch |first2=Edmund A. |last3=Latimer |first3=Heejeong |last4=Kadry |first4=Abdel-Razak |last5=Kause |first5=Janell |date=July 2009 |title=Risk Assessment for Clostridium perfringens in Ready-to-Eat and Partially Cooked Meat and Poultry Products |journal=Journal of Food Protection |volume=72 |issue=7 |pages=1376–1384 |doi=10.4315/0362-028x-72.7.1376 |pmid=19681258 |issn=0362-028X|doi-access=free }}</ref> The electric pulse creates pores in the bacterial cell membrane and allows the passive influx of DNA molecules.<ref>{{Cite journal |last1=Rood |first1=J I |last2=Cole |first2=S T |date=1991 |title=Molecular genetics and pathogenesis of Clostridium perfringens. |journal=Microbiological Reviews |language=en |volume=55 |issue=4 |pages=621–648 |doi=10.1128/MMBR.55.4.621-648.1991 |issn=0146-0749|doi-access=free |pmid=1779929 |pmc=372840 }}</ref>

== Metabolic processes ==
''C. perfringens'' is an aerotolerant anaerobe bacterium that lives in a variety of environments including soil and human intestinal tract.<ref name="Ohtani-2016">{{Cite journal |last1=Ohtani |first1=Kaori |last2=Shimizu |first2=Tohru |date=2016-07-05 |title=Regulation of Toxin Production in Clostridium perfringens |journal=Toxins |language=en |volume=8 |issue=7 |pages=207 |doi=10.3390/toxins8070207 |pmid=27399773 |issn=2072-6651|doi-access=free |pmc=4963840 }}</ref> ''C. perfringens'' is incapable of synthesizing multiple amino acids due to the lack of genes required for biosynthesis.<ref name="Ohtani-2016" /> Instead, the bacterium produces enzymes and toxins to break down host cells and import nutrients from the degrading cell.<ref name="Ohtani-2016" />

''C. perfringens'' has a complete set of [[enzyme]]s for [[glycolysis]] and [[glycogen]] metabolism. In the fermentation pathway, [[pyruvate]] is converted into [[acetyl-CoA]] by [[pyruvate-ferredoxin oxidoreductase]], producing [[Carbon dioxide|CO2]] gas and reduced [[ferredoxin]].<ref name="ReferenceA">{{Cite journal |last1=Shimizu |first1=Tohru |last2=Ohtani |first2=Kaori |last3=Hirakawa |first3=Hideki |last4=Ohshima |first4=Kenshiro |last5=Yamashita |first5=Atsushi |last6=Shiba |first6=Tadayoshi |last7=Ogasawara |first7=Naotake |last8=Hattori |first8=Masahira |last9=Kuhara |first9=Satoru |last10=Hayashi |first10=Hideo |date=2002-01-22 |title=Complete genome sequence of Clostridium perfringens , an anaerobic flesh-eater |journal=Proceedings of the National Academy of Sciences |language=en |volume=99 |issue=2 |pages=996–1001 |doi=10.1073/pnas.022493799 |doi-access=free |issn=0027-8424 |pmc=117419 |pmid=11792842|bibcode=2002PNAS...99..996S }}</ref> Electrons from the reduced ferredoxin are transferred to protons by hydrogenase, resulting in the formation of hydrogen molecules (H2) that are released from the cell along with [[Carbon dioxide|CO2]]. Pyruvate is also converted to [[Lactic acid|lactate]] by [[lactate dehydrogenase]], whereas acetyl-CoA is converted into [[ethanol]], [[acetate]], and [[butyrate]] through various enzymatic reactions, completing the [[anaerobic glycolysis]] that serves as a potential main energy source for ''C. perfringens''. ''C. perfringens'' utilizes a variety of sugars such as [[fructose]], [[galactose]], [[glycogen]], [[lactose]], [[maltose]], [[mannose]], [[raffinose]], [[starch]], and [[sucrose]], and various genes for [[Glycolysis|glycolytic]] enzymes. The amino acids of these various enzymes and sugar molecules are converted to [[propionate]] through [[propionyl-CoA]], which results in energy production.<ref name="ReferenceA"/>

== Virulence ==
Membrane-damaging enzymes, pore-forming toxins, intracellular toxins, and hydrolytic enzymes are the functional categories into which ''C. perfringens''<nowiki/>' virulence factors may be divided. These virulence factor-encoding genes can be found on chromosomes and large plasmids.<ref name="Revitt-Mills-20152"/>

=== Carbohydrate-active enzymes ===
The human gastrointestinal tract is lined with [[Gastrointestinal wall|intestinal mucosa]] that secrete [[mucus]] and act as a defense mechanism against pathogens, toxins, and harmful substances. Mucus is made up of [[mucin]]s containing several [[O-linked glycosylation|O-linked glycan]] [[glycoprotein]]s that recognizes and forms a barrier around microbes, preventing them from attaching to endothelial cells and infecting them.<ref>{{Cite journal |last1=Ba |first1=Xuli |last2=Jin |first2=Youshun |last3=Ning |first3=Xuan |last4=Gao |first4=Yidan |last5=Li |first5=Wei |last6=Li |first6=Yunhui |last7=Wang |first7=Yihan |last8=Zhou |first8=Jizhang |date=2024-08-07 |title=Clostridium perfringens in the Intestine: Innocent Bystander or Serious Threat? |journal=Microorganisms |language=en |volume=12 |issue=8 |pages=1610 |doi=10.3390/microorganisms12081610 |issn=2076-2607 |pmc=11356505 |pmid=39203452 |doi-access=free}}</ref><ref name=":022">{{Cite journal |last1=Low |first1=Kristin E |last2=Smith |first2=Steven P |last3=Abbott |first3=D Wade |last4=Boraston |first4=Alisdair B |date=2020-05-30 |title=The glycoconjugate-degrading enzymes of ''Clostridium perfringens'': Tailored catalysts for breaching the intestinal mucus barrier |url=https://academic.oup.com/glycob/article/31/6/681/5848600 |journal=Glycobiology |volume=31 |issue=6 |pages=681–690 |doi=10.1093/glycob/cwaa050 |issn=1460-2423 |pmid=32472136|url-access=subscription }}</ref> ''C. perfringens'' can secrete different [[CAZy|carbohydrate-active enzymes]] (CAZymes) that aid in degrading mucins and other O-glycans within the intestinal mucosa. These enzymes include: Sialidases, Hexosaminidases, Galactosidases, and Fucosidases belonging to various [[glycoside hydrolase families]].<ref name=":022" />

==== Sialidase ====
[[Neuraminidase|Sialidases]], also called neuraminidases, function to breakdown mucin by [[Hydrolysis|hydrolyzing]] the terminal sialic acid residues located within the protein through the process of [[Desilylation|desialylation]]. ''C. perfringens'' has three sialidases belonging to [[Glycoside hydrolase family 33|glycoside hydrolase family 33 (GH33)]]: NanH, NanI, and NanJ. All strains of ''C. perfringens'' encode for at least one of these enzymes.<ref name=":022" /><ref>{{Cite journal |last1=Medley |first1=Brendon J. |last2=Low |first2=Kristin E. |last3=Irungu |first3=Jackline D. W. |last4=Kipchumba |first4=Linus |last5=Daneshgar |first5=Parandis |last6=Liu |first6=Lin |last7=Garber |first7=Jolene M. |last8=Klassen |first8=Leeann |last9=Inglis |first9=G. Douglas |last10=Boons |first10=Geert-Jan |last11=Zandberg |first11=Wesley F. |last12=Abbott |first12=D. Wade |last13=Boraston |first13=Alisdair B. |date=2024-10-01 |title=A "terminal" case of glycan catabolism: Structural and enzymatic characterization of the sialidases of Clostridium perfringens |journal=Journal of Biological Chemistry |volume=300 |issue=10 |pages=107750 |doi=10.1016/j.jbc.2024.107750 |doi-access=free |pmid=39251137 |pmc=11525138 |bibcode=2024JBiCh.300j7750M |issn=0021-9258}}</ref>

''C. perfringens'' can secrete NanI and NanJ through secretion signal [[peptide]]s located on each protein. Research suggests that NanH operates in the cytoplasm of ''C. perfringens'', as it does not contain a secretion signal peptide. NanH contains only a catalytic domain, whereas NanI and NanJ contain a [[catalytic domain]] and additional [[carbohydrate-binding module]]s (CBMs) to aid in catalytic activity. Located on their N-terminals, NanI contains CBM40, whereas NanJ contains both CBM40 and CBM32. Based on studies analyzing the three-dimensional structure of NanI, its [[active site]] has a pocket-like orientation that aids in the removal of sialic acid residues from sialomucins in the intestinal mucosa.<ref name=":022" />

==== Hexosaminidase ====
The mucus layer consists of intestinal mucin glycans, glycolipids, and glycoproteins that contain [[hexosamines]], such as [[N-Acetylglucosamine|N-acetylglucosamine]] (GlcNAc) and [[N-Acetylgalactosamine|N-acetylgalactosamine]] (GalNAc). ''C. perfringens'' encodes for eight [[hexosaminidase]]s that break down hexosamines in the mucus. These hexosaminidases belong to four glycoside hydrolase families: GH36, GH84, GH89, and GH123.<ref name=":022" />

''C. perfringens'' encodes for AagA (''Cp''GH36A) and ''Cp''GH36B in [[Glycoside hydrolase family 36|glycoside hydrolase family 36 (GH36)]]: AagA removes GalNAc from O-glycans, and ''Cp''GH36B is expected to have a similar structure to AagA, but specificities on its function are unknown. NagH, NagI, NagJ, and NagK, belonging to glycoside hydrolase family 84 (GH84), cleave terminal GlcNAc residues using a substrate-assisted digestion mechanism. AgnC (''Cp''GH89), belonging to [[glycoside hydrolase family 89]] (GH89), both cleaves GlcNAc from the ends of mucin glycans and acts on gastric mucin. Belonging to glycoside hydrolase family 123 (GH123), ''Cp''Nga123 cleaves GalNAc, but research suggests that it only breaks down glycans taken up by ''C. perfringens'' due to the absence of a secretion signal peptide.<ref name=":022" />

==== Galactosidase ====
''C. perfringens'' has four [[galactosidases]] that belong to the [[glycoside hydrolase family 2|glycoside hydrolase family 2 (GH2)]]: ''Cp''GH2A, ''Cp''GH2B, ''Cp''GH2C, and ''Cp''GH2D. Research suggests that these enzymes are effective at breaking down core mucin glycan structures with the ability to bind [[galactose]] using CBM51. However, minimal research exists on the specific functioning of galactosidases in ''C. perfringens''.<ref name=":022" />

==== Fucosidase ====
[[Fucose]] monosaccharides are located on the terminal ends of core O-linked glycans. ''C. perfringens'' encodes for three fucosidases that belong to two glycoside hydrolase families: Afc1 and Afc2 in [[glycoside hydrolase family 29]] (GH29), and Afc3 in glycoside hydrolase family 95 (GH95). Afc3 contains a C-terminal CBM51 and is the only fucosidase that contains a carbohydrate-binding module in ''C. perfringens''. Fucosyl residues tend to cover the ends of glycans and protect them against enzymatic digestion, so research suggests that the ability of fucosidases to cleave complex and diverse fucosyl linkages is due to long-term adaptations in ''C. perfringens'' that persisted within close range of mucins.<ref name=":022" />

=== 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>
! {{diagonal split header|Type|Toxin}} 
!Alpha
!Beta
!Epsilon
!Iota
!Enterotoxin
!NetB
!Notes
|-
! scope="row" |A
| {{yes|+}} || {{no|-}} || {{no|-}}
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|-
! scope="row" |B
| {{yes|+}} || {{yes|+}} || {{no|-}} || {{no|-}}
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|-
! scope="row" |C
| {{yes|+}} || {{yes|+}} || {{no|-}} || {{partial|+/-}} || {{no|-}}
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|-
! scope="row" |D
| {{yes|+}} || {{no|-}} || {{yes|+}} || {{no|-}} || {{partial|+/-}} || {{no|-}}
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|-
! scope="row" |E
| {{yes|+}} || {{no|-}} || {{yes|+}} || {{partial|+/-}} || {{no|-}}
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|-
! scope="row" |F
| {{yes|+}} || {{no|-}} || {{yes|+}} || {{no|-}}
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|-
! scope="row" |G
| {{yes|+}} || {{no|-}} || {{yes|+}}
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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>

=== Other toxins ===
TpeL is a toxin found in type B, C, and G<ref name="pmid340765062">{{cite journal |last1=Orrell |first1=KE |last2=Melnyk |first2=RA |date=18 August 2021 |title=Large Clostridial Toxins: Mechanisms and Roles in Disease. |journal=Microbiology and Molecular Biology Reviews |volume=85 |issue=3 |pages=e0006421 |doi=10.1128/MMBR.00064-21 |pmc=8483668 |pmid=34076506}}</ref> strains. It is in the same [[protein family]] as [[Clostridium difficile toxin A|''C. difficile'' toxin A]].<ref>{{cite journal |last1=Chen |first1=J |last2=McClane |first2=BA |date=June 2015 |title=Characterization of Clostridium perfringens TpeL toxin gene carriage, production, cytotoxic contributions, and trypsin sensitivity. |journal=Infection and Immunity |volume=83 |issue=6 |pages=2369–81 |doi=10.1128/IAI.03136-14 |pmc=4432761 |pmid=25824828}}</ref> It does not appear important in the pathogenesis of types B and C infections, but may contribute to virulence in type G strains. It glycosylates Rho and [[Ras GTPase]]s, disrupting host cell signaling.<ref name="pmid340765062" />

==Infection==
Tissue [[necrosis]], [[bacteremia]], emphysematous [[cholecystitis]], and [[gas gangrene]], also known as clostridial [[myonecrosis]], have been linked to infections associated with ''C. perfringens''.<ref name=":32" /> Research suggests that ''C. perfringens'' is capable of engaging in polymicrobial [[anaerobic infection]]s.<ref name=":42">{{Cite journal |last1=Takehara |first1=Masaya |last2=Takagishi |first2=Teruhisa |last3=Seike |first3=Soshi |last4=Ohtani |first4=Kaori |last5=Kobayashi |first5=Keiko |last6=Miyamoto |first6=Kazuaki |last7=Shimizu |first7=Tohru |last8=Nagahama |first8=Masahiro |date=2016-06-16 |title=Clostridium perfringens α-Toxin Impairs Innate Immunity via Inhibition of Neutrophil Differentiation |journal=Scientific Reports |language=en |volume=6 |issue=1 |page=28192 |bibcode=2016NatSR...628192T |doi=10.1038/srep28192 |issn=2045-2322 |pmc=4910053 |pmid=27306065}}</ref>

''Clostridium perfringens'' is a common cause of food poisoning in the United States. ''C. perfringens'' produces spores, and when these [[spore]]s are consumed, they produce a toxin that causes diarrhea. Foods cooked in large batches and held at unsafe temperatures (between 40&nbsp;°F and 140&nbsp;°F) are the source of ''C. perfringens'' food poisoning outbreaks. Meats such as poultry, beef, and pork are commonly linked to ''C. perfringens'' food poisoning.<ref>{{Cite web |last=CDC |date=2024-05-16 |title=About C. perfringens food poisoning |url=https://www.cdc.gov/clostridium-perfringens/about/index.html |access-date=2024-11-20 |website=Clostridium perfringens Food Poisoning |language=en-us}}</ref> ''C. perfringens'' can proliferate in foods that are improperly stored due to the spore's ability to survive normal cooking temperatures. The type A toxin of ''C. perfringens'', also known as the CPA is responsible for food poisoning.<ref>{{Citation |last1=Yao |first1=Phil Y. |title=Clostridium perfringens Infection |date=2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK559049/ |access-date=2024-11-20 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32644475 |last2=Annamaraju |first2=Pavan}}</ref>

''Clostridium perfringens'' is the most common bacterial agent for [[gas gangrene]].<ref name=":2">{{cite web |title=Gas gangrene: MedlinePlus Medical Encyclopedia |url=https://medlineplus.gov/ency/article/000620.htm}}</ref> Gas gangrene is induced by [[Clostridium perfringens alpha toxin|α-toxin]] that embeds itself into the plasma membrane of cells and disrupts normal cellular function by altering membrane structure.<ref name=":32"/> Some symptoms include blisters, tachycardia, swelling, and jaundice.<ref name=":2" />

''C. perfringens'' is most commonly known for foodborne illness but can translocate from a gastrointestinal source into the bloodstream which causes [[bacteremia]]. ''C. perfringens'' bacteremia can lead to toxin-mediated intravascular hemolysis and septic shock.<ref>{{Cite journal |date=2023-06-03 |title=Cytarabine |url=http://dx.doi.org/10.1007/s40278-023-40395-7 |journal=Reactions Weekly |volume=1959 |issue=1 |pages=223 |doi=10.1007/s40278-023-40395-7 |issn=1179-2051 |s2cid=259027022|url-access=subscription }}</ref> This is rare as it makes up less than 1% of bloodstream isolates but is highly fatal with a reported mortality rate of 27% to 58%.<ref>{{Cite journal |last1=Millard |first1=Michael A. |last2=McManus |first2=Kathleen A. |last3=Wispelwey |first3=Brian |date=2016 |title=Severe Sepsis due to Clostridium perfringens Bacteremia of Urinary Origin: A Case Report and Systematic Review |journal=Case Reports in Infectious Diseases |language=en |volume=2016 |pages=1–5 |doi=10.1155/2016/2981729 |issn=2090-6625 |pmc=4779822 |pmid=26998370 |doi-access=free}}</ref>

''Clostridium perfringens'' food poisoning can also lead to another disease known as enteritis necroticans or [[clostridial necrotizing enteritis]], (also known as pigbel); this is caused by ''C. perfringens'' type C. This infection is often fatal. Large numbers of ''C. perfringens'' grow in the intestines and secrete exotoxin. This exotoxin causes necrosis of the intestines, varying levels of hemorrhaging, and perforation of the intestine. Inflammation usually occurs in sections of the jejunum, midsection of the small intestine.<ref name="Lentino-2016">{{Cite web |last=Lentino |first=Joseph R. |date=2016-01-01 |title=Clostridial Necrotizing Enteritis |url=http://www.merckmanuals.com/professional/infectious-diseases/anaerobic-bacteria/clostridial-necrotizing-enteritis |access-date=2016-09-27 |website=Merck Manuel |publisher=Merck Sharp & Dohme Corp.}}</ref> [[Cytolysin|Perfringolysin O]] (''pfoA'')-positive ''C. perfringens'' strains were also associated with the rapid onset of [[necrotizing enterocolitis]] in preterm infants.<ref>{{Cite journal |last1=Kiu |first1=Raymond |last2=Shaw |first2=Alexander G. |last3=Sim |first3=Kathleen |last4=Acuna-Gonzalez |first4=Antia |last5=Price |first5=Christopher A. |last6=Bedwell |first6=Harley |last7=Dreger |first7=Sally A. |last8=Fowler |first8=Wesley J. |last9=Cornwell |first9=Emma |last10=Pickard |first10=Derek |last11=Belteki |first11=Gusztav |last12=Malsom |first12=Jennifer |last13=Phillips |first13=Sarah |last14=Young |first14=Gregory R. |last15=Schofield |first15=Zoe |date=June 2023 |title=Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains |journal=Nature Microbiology |language=en |volume=8 |issue=6 |pages=1160–1175 |doi=10.1038/s41564-023-01385-z |issn=2058-5276 |pmc=10234813 |pmid=37231089}}</ref>

A strain of ''C. perfringens'' might be implicated in [[multiple sclerosis]] (MS) nascent ([[Balo concentric sclerosis|Pattern III]]) lesions.<ref>{{cite journal |last1=Rumah |first1=Kareem Rashid |last2=Linden |first2=Jennifer |last3=Fischetti |first3=Vincent A. |last4=Vartanian |first4=Timothy |last5=Esteban |first5=Francisco J. |date=16 October 2013 |title=Isolation of Clostridium perfringens Type B in an Individual at First Clinical Presentation of Multiple Sclerosis Provides Clues for Environmental Triggers of the Disease |journal=PLOS ONE |volume=8 |issue=10 |pages=e76359 |bibcode=2013PLoSO...876359R |doi=10.1371/journal.pone.0076359 |pmc=3797790 |pmid=24146858 |doi-access=free}}</ref> Tests in [[Laboratory mouse|mice]] found that two strains of intestinal ''C. perfringens'' that produced epsilon toxins (ETX) caused MS-like damage in the brain, and earlier work had identified this strain of ''C. perfringens'' in a human with MS.<ref>{{cite web |date=29 January 2014 |title=Multiple sclerosis 'linked to food bug' |url=https://www.bbc.co.uk/news/health-25925658 |access-date=29 January 2014 |publisher=BBC}}</ref><ref>{{Cite journal |last=Reder |first=Anthony T. |date=2023-05-01 |title=Clostridium epsilon toxin is excessive in multiple sclerosis and provokes multifocal lesions in mouse models |journal=Journal of Clinical Investigation |language=en |volume=133 |issue=9 |doi=10.1172/JCI169643 |issn=1558-8238 |pmc=10145922 |pmid=37115699 |s2cid=258375399 |doi-access=free}}</ref> MS patients were found to be 10 times more likely<ref>{{cite journal |last1=Rumah |first1=Kareem Rashid |last2=Linden |first2=Jennifer |last3=Fischetti |first3=Vincent A. |last4=Vartanian |first4=Timothy |title=Isolation of Clostridium perfringens Type B in an Individual at First Clinical Presentation of Multiple Sclerosis Provides Clues for Environmental Triggers of the Disease |journal=PLOS ONE |date=16 October 2013 |volume=8 |issue=10 |pages=e76359 |doi=10.1371/journal.pone.0076359|doi-access=free |pmid=24146858 |pmc=3797790 |bibcode=2013PLoSO...876359R }}</ref> to be immune-reactive to the epsilon toxin than healthy people.<ref>{{cite web |last=Woerner |first=Amanda |date=29 January 2014 |title=Bacterial toxin may trigger multiple sclerosis, research finds |url=https://www.foxnews.com/health/bacterial-toxin-may-trigger-multiple-sclerosis-research-finds/?intcmp=trending |website=[[Fox News]]}}</ref> Greatly increased rates of gut colonization by type B and D ''C. perfringens'' are seen in MS patients.<ref>{{cite journal |last1=Reder |first1=AT |title=Clostridium epsilon toxin is excessive in multiple sclerosis and provokes multifocal lesions in mouse models. |journal=The Journal of Clinical Investigation |date=1 May 2023 |volume=133 |issue=9 |doi=10.1172/JCI169643 |pmid=37115699 |pmc=10145922}}</ref>

Tissue gas occurs when ''C. perfringens'' infects corpses. It causes extremely accelerated decomposition and can only be stopped by [[embalming]] the corpse. Tissue gas most commonly occurs to those who have died from gangrene, large [[decubitus]] ulcers, necrotizing fasciitis or to those who had soil, feces, or water contaminated with ''C. perfringens'' forced into an open wound.<ref>{{cite web |title=Clostridium perfringens |url=https://ldh.la.gov/assets/oph/Center-PHCH/Center-CH/infectious-epi/EpiManual/ClostridiumPerfringensManual.pdf |website=ldh.la.gov/ |publisher=Louisiana Office of Public Health |access-date=14 June 2024}}</ref>

== Clinical manifestations ==
''Clostridium perfringens'' infections can lead to various clinical manifestations, ranging from mild gastrointestinal symptoms to life-threatening conditions. The most common presentation is food poisoning, characterized by acute abdominal pain, diarrhea, and, in some cases, vomiting, typically occurring 6 to 24 hours after the ingestion of contaminated food. Unlike many other foodborne illnesses, fever is usually absent. Symptoms are usually self-limiting and resolve within 24 to 48 hours; however, severe dehydration can occur in cases of significant fluid loss. Symptoms of dehydration include dry mouth, decreased urine output, dizziness, and fatigue. Severe symptoms such as diarrhea that persists for more than 48 hours, the inability to keep fluids down, or signs of severe dehydration may necessitate medical attention.<ref>{{cite web |title=Symptoms of C. perfringens food poisoning |url=https://www.cdc.gov/clostridium-perfringens/signs-symptoms/index.html#:~:text=Most%20people%20with%20C.%20perfringens%20food%20poisoning%20have,should%20drink%20plenty%20of%20fluids%20to%20prevent%20dehydration. |access-date=12 November 2024 |website=Centers for Disease Control and Prevention| date=13 May 2024 }}</ref> Most people are able to recover from ''C. perfringens'' food poisoning without treatment. However, people who experience diarrhea are usually instructed to drink water or rehydration solutions.<ref>{{Cite web |last=CDC |date=2024-05-13 |title=Treating C. perfringens food poisoning |url=https://www.cdc.gov/clostridium-perfringens/treatment/index.html |access-date=2024-11-20 |website=Clostridium perfringens Food Poisoning |language=en-us}}</ref>

Gas gangrene caused by ''Clostridium perfringens'' is characterized by severe symptoms, including intense pain at the injury site, fever, rapid heart rate, sweating, and anxiety. The affected area may show signs of swelling, discoloration (ranging from pale to dark red or purplish), and large, discolored blisters filled with foul-smelling fluid. As the toxins spread, skin and muscle tissue are rapidly destroyed, leading to large areas of dead tissue, gas pockets under the skin (crepitus), and possible [[renal failure]] due to red blood cell destruction. [[Sepsis]] and [[septic shock]] may also occur, which can be fatal.<ref name=":5">{{Cite web |date=February 2024 |title=Gas Gangrene |url=https://my.clevelandclinic.org/health/diseases/24739-gas-gangrene |website=Cleveland Clinic}}</ref>

Necrotizing enteritis caused by ''Clostridium perfringens'' presents with a wide range of symptoms, which can vary in severity. The clinical signs range from mild diarrhea to more severe manifestations such as intense abdominal pain, vomiting, bloody stools, and even septic shock. In the most serious cases, the infection can lead to death.<ref name=":6">{{Cite web |title=Clostridial Necrotizing Enteritis - Clostridial Necrotizing Enteritis |url=https://www.msdmanuals.com/professional/infectious-diseases/anaerobic-bacteria/clostridial-necrotizing-enteritis?ruleredirectid=748 |access-date=2024-11-21 |website=MSD Manual Professional Edition |language=en}}</ref>

== Diagnosis ==
The diagnosis of ''Clostridium perfringens'' food poisoning relies on laboratory detection of the bacterium or its toxin in either a patient’s stool sample or contaminated food linked to the illness. A positive stool culture would have growth of at least 10 cfu/g of C. ''perfringens''. Stool studies include [[White blood cell|WBCs]], [[Egg cell|ova]], and parasites in order to rule out other potential [[etiologies]]. [[ELISA]] testing is used to detect the CPA toxin. Diagnosing ''C. perfringens'' food poisoning is relatively uncommon for several reasons.<ref>{{Citation |last1=Yao |first1=Phil Y. |title=Clostridium perfringens Infection |date=2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK559049/ |access-date=2024-11-21 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32644475 |last2=Annamaraju |first2=Pavan}}</ref> Most individuals with this foodborne illness do not seek medical care or submit a stool sample for testing, and routine testing for ''C. perfringens'' is not typically performed in clinical laboratories. Additionally, public health laboratories generally conduct testing for this pathogen only in the event of an outbreak.<ref>{{Cite web |last=CDC |date=2024-05-13 |title=Diagnosing C. perfringens food poisoning |url=https://www.cdc.gov/clostridium-perfringens/testing/index.html |access-date=2024-11-21 |website=Clostridium perfringens Food Poisoning |language=en-us}}</ref>

The diagnosis of gas gangrene typically involves several methods to confirm the infection. Imaging techniques such as [[X-ray]]s, [[CT scan]]s, or [[Magnetic resonance imaging|MRIs]] can reveal gas bubbles or tissue changes indicative of muscle damage. Additionally, bacterial staining or culture of fluid taken from the wound helps identify ''Clostridium perfringens'' and other bacteria responsible for the infection. In some cases, a [[biopsy]] is performed, where a sample of the affected tissue is analyzed for signs of damage or necrosis.<ref name=":5" />

The diagnosis of clostridial necrotizing enteritis is primarily based on the patient's clinical symptoms, which can include severe abdominal pain, vomiting, and bloody diarrhea. Additionally, confirmation of the presence of ''Clostridium perfringens'' [[Toxin-antitoxin system|type C toxin]] in stool samples is crucial for accurate diagnosis.<ref name=":6" />

== Epidemiology ==
''Clostridium perfringens'' is responsible for an estimated 966,000 cases annually, or about 10.3% of all foodborne illnesses in which a pathogen is identified. Transmission typically occurs when food contaminated with ''C. perfringens'' spores is consumed, allowing the bacteria to produce a toxin in the intestines that causes diarrhea. Outbreaks are often associated with foods cooked in large batches, such as poultry, meat, and gravy, and held at unsafe temperatures between 40-140&nbsp;°F, which allows the bacteria to thrive. These outbreaks tend to occur in settings where large groups are served, such as hospitals, school cafeterias, prisons, nursing homes, and catered events. In most cases, ''C. perfringens'' infection causes mild symptoms, including watery diarrhea and mild abdominal cramps, with symptoms typically appearing 8 to 12 hours after consuming contaminated food and resolving within 24 hours. About 90% of affected individuals recover without seeking medical attention, usually within two days. However, vulnerable groups such as the elderly, young children, and immunocompromised individuals face a higher risk of severe complications like dehydration, which can lead to more serious illness or, in rare cases, death. Each year, ''C. perfringens'' infections result in approximately 438 hospitalizations and 26 deaths, accounting for 0.8% of foodborne illness-related hospitalizations and 1.9% of associated deaths. Outbreaks are most common in November and December, coinciding with holiday foods like turkey and roast beef. The economic burden of ''C. perfringens'' is significant, estimated at $342.7 million annually, including $53.2 million in medical costs, $64.3 million in productivity loss, and $225 million related to fatalities.<ref>{{Cite web |last1=Hoffmann |first1=Sandra |last2=Maculloch |first2=Bryan |last3=Batz |first3=Michael |title=Economic Burden of Major Foodborne Illnesses Acquired in the United States |url=https://www.ers.usda.gov/publications/pub-details/?pubid=43987 |access-date=2024-11-21 |website=www.ers.usda.gov |language=en}}</ref><ref>{{Cite web |last=CDC |date=2024-05-16 |title=About C. perfringens food poisoning |url=https://www.cdc.gov/clostridium-perfringens/about/index.html#:~:text=Clostridium%20perfringens%20bacteria%20are%20a%20common%20cause%20of,C.%20perfringens%20makes%20spores,%20which%20have%20protective%20coatings. |access-date=2024-11-21 |website=Clostridium perfringens Food Poisoning |language=en-us}}</ref>

Clostridial necrotizing enteritis is rare in the United States; typically, it occurs in populations with a higher risk. Data show that of the 9.4 million cases of foodborne illness in the United States each year, only about 11% are caused by ''Clostridium perfringens''.<ref>{{Cite journal |last1=Scallan |first1=Elaine |last2=Hoekstra |first2=Robert M. |last3=Angulo |first3=Frederick J. |last4=Tauxe |first4=Robert V. |last5=Widdowson |first5=Marc-Alain |last6=Roy |first6=Sharon L. |last7=Jones |first7=Jeffery L. |last8=Griffin |first8=Patricia M. |date=January 2011 |title=Foodborne Illness Acquired in the United States—Major Pathogens |journal=Emerging Infectious Diseases |language=en |volume=17 |issue=1 |pages=7–15 |doi=10.3201/eid1701.P11101 |pmc=3375761 |pmid=21192848}}</ref> "Risk factors for [[enteritis necroticans]] include protein-deficient diet, unhygienic food preparation, sporadic feasts of meat (after long periods of a protein-deficient diet), diets containing large amounts of [[trypsin]] inhibitors ([[sweet potatoes]]), and areas prone to infection of the parasite ''[[Ascaris]]'' (produces a trypsin inhibitor). This disease is contracted in populations living in New Guinea, parts of Africa, Central America, South America, and Asia.<ref name="Lentino-2016" />

Risk factors for gas gangrene include severe injuries, abdominal surgeries, and underlying health conditions such as [[colon cancer]], diseases of the blood vessels, [[diabetes]], and [[diverticulitis]]. However, the most common way to get gas gangrene is through a traumatic injury. In the United States, there is only about 1000 cases of gas gangrene per year. When addressed with adequate care, gas gangrene has a mortality rate of 20-30% but has a mortality rate of 100% if left untreated.<ref>{{Citation |last1=Buboltz |first1=Jerome B. |title=Gas Gangrene |date=2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK537030/ |access-date=2024-11-21 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30725715 |last2=Murphy-Lavoie |first2=Heather M.}}</ref>

== Food poisoning incidents ==
On May 7, 2010, 42 residents and 12 staff members at a Louisiana (USA) state psychiatric hospital were affected and experienced vomiting, abdominal cramps, and diarrhea. Three patients died within 24 hours. The outbreak was linked to chicken which was cooked a day before it was served and was not cooled down according to hospital guidelines. The outbreak affected 31% of the residents of the hospital and 69% of the staff who ate the chicken. How many of the affected residents ate the chicken is unknown.<ref>{{cite web |title=Fatal Foodborne Clostridium perfringens Illness at a State Psychiatric Hospital — Louisiana, 2010 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6132a1.htm |access-date=16 November 2013 |work=Centers for Disease Control and Prevention}}</ref>

In May 2011, a man died after allegedly eating food contaminated with the bacteria on a [[Transatlantic flight|transatlantic]] [[American Airlines]] flight. The man's wife and daughter were suing American and [[LSG Sky Chefs]], the German company that prepared the inflight food.<ref>{{cite web |last=Mohn |first=Tanya |date=1 December 2011 |title=Passenger dies in-flight, family says airline to blame |url=http://overheadbin.nbcnews.com/_news/2011/12/01/9146822-passenger-dies-in-flight-family-says-airline-to-blame?chromedomain=usnews |access-date=2012-02-13 |website=Overhead Bin |publisher=MSNBC}}</ref>

In December 2012, a 46-year-old woman died two days after eating a Christmas Day meal at a pub in [[Hornchurch]], [[Essex]], England. She was among about 30 people to fall ill after eating the meal. Samples taken from the victims contained ''C. perfringens''. The hotel manager and the cook were jailed for forging cooking records relating to the cooking of the turkey.<ref>{{cite news |date=23 January 2015 |title=Pub chef and manager jailed over Christmas dinner that left a diner dead |url=https://www.theguardian.com/uk-news/2015/jan/23/pub-chef-manager-jailed-christmas-dinner-diner-dead |access-date=3 August 2015 |work=[[The Guardian]]}}</ref>

In December 2014, 87-year-old Bessie Scott died three days after eating a church potluck supper in [[Nackawic]], [[New Brunswick]], Canada. Over 30 other people reported signs of gastrointestinal illness, diarrhea, and abdominal pain. The province's acting chief medical officer says, ''Clostridium perfringens'' is the bacteria [sic] that most likely caused the woman's death.<ref>{{cite news |date=12 December 2014 |title=Woman's death likely caused by bacteria from Christmas supper |url=http://www.cbc.ca/news/canada/new-brunswick/woman-s-death-likely-caused-by-bacteria-from-christmas-supper-1.2870869 |publisher=[[Canadian Broadcasting Corporation|CBC]]}}</ref>

In October 2016, 66-year-old Alex Zdravich died four days after eating an enchilada, burrito, and taco at Agave Azul in [[West Lafayette, Indiana]], United States. Three others who dined the same day reported signs of foodborne illness, which were consistent with the symptoms and rapid onset of ''C. perfringens'' infection. They later tested positive for the presence of the bacteria, but the leftover food brought home by Zdravich tested negative.<ref>{{Cite news |date=2017-07-17 |title=Food poisoning death at Indiana restaurant kept secret for months |url=http://www.wthr.com/article/food-poisoning-death-at-indiana-restaurant-kept-secret-for-months |url-status=dead |archive-url=https://web.archive.org/web/20170720195249/http://www.wthr.com/article/food-poisoning-death-at-indiana-restaurant-kept-secret-for-months |archive-date=2017-07-20 |access-date=2017-07-18 |work=13 WTHR Indianapolis}}</ref><ref>{{Cite web |last=(WTHR) |first=Susan Batt |title=Agave Azul Tippecanoe Co Food Poisoning Finding Summary |url=https://www.documentcloud.org/documents/3896503-Agave-Azul-Tippecanoe-Co-Food-Poisoning-Finding.html |access-date=2017-07-18 |website=www.documentcloud.org |language=en}}</ref>

In November 2016, food contaminated with ''C. perfringens'' caused three individuals to die, and another 22 to be sickened, after a [[Thanksgiving (United States)|Thanksgiving]] luncheon hosted by a church in [[Antioch, California]], United States.<ref>{{Cite news |title=Bacteria that killed 3 at Antioch Thanksgiving dinner pinpointed |url=http://www.sfgate.com/bayarea/article/Bacteria-that-killed-3-at-Antioch-Thanksgiving-10808875.php |access-date=2016-12-20 |newspaper=SFGate}}</ref>

In January 2017, a mother and her son sued a restaurant in [[Rochester, New York]], United States, as they and 260 other people were sickened after eating foods contaminated with ''C. perfringens''. "Officials from the Monroe County Department of Public Health closed down the Golden Ponds after more than a fourth of its Thanksgiving Day guests became ill. An inspection revealed a walk-in refrigerator with food spills and mold, a damaged gasket preventing the door from closing, and mildew growing inside."<ref>{{cite web |date=6 January 2017 |title=Mother, son sue eatery for Thanksgiving dinner food poisoning - Food Safety News |url=http://www.foodsafetynews.com/2017/01/mother-son-sue-eatery-for-thanksgiving-dinner-food-poisoning/#.WPeAKIgrKM8}}</ref>

In July 2018, 647 people reported symptoms after eating at a [[Chipotle Mexican Grill]] restaurant in [[Powell, Ohio]], United States. Stool samples tested by the [[Centers for Disease Control and Prevention|CDC]] tested positive for ''C. perfringens''.<ref>{{cite web |date=16 August 2018 |title=CDC releases test findings after hundreds sickened at Powell Chipotle - Columbus Dispatch |url=http://www.dispatch.com/business/20180816/cdc-releases-test-findings-after-hundreds-sickened-at-powell-chipotle |url-status=dead |archive-url=https://web.archive.org/web/20180816201052/http://www.dispatch.com/business/20180816/cdc-releases-test-findings-after-hundreds-sickened-at-powell-chipotle |archive-date=16 August 2018 |access-date=16 August 2018}}</ref>

In November 2018, approximately 300 people in Concord, [[North Carolina]], United States, were sickened by food at a church barbecue that tested positive for ''C. perfringens''.<ref>{{Cite news |date=November 2018 |title=Strain of food poisoning causes illness at North Carolina church barbecue |url=https://myfox8.com/2018/11/17/strain-of-food-poisoning-causes-illness-at-north-carolina-church-barbecue/amp/}}</ref>

In 2021, a foodborne illness outbreak in [[Homer, Alaska]], affected approximately 80 employees of South Peninsula Hospital and was traced to Cubano sandwiches served during staff meals. The [[Alaska Department of Health and Social Services]] identified the likely cause as ''C. perfringens''. No hospitalizations were reported, and the outbreak was contained to hospital staff. Such localized outbreaks are considered uncommon in Alaska when not tied to a national foodborne incident.<ref>{{Cite web |date=August 12, 2021 |title=Cubano Sandwiches with Clostridium Perfringens Found in Alaska Investigation |url=https://www.foodsafetynews.com/2021/08/cubano-sandwiches-with-clostridium-perfringens-found-in-alaska-investigation/. |website=Food Safety News}}</ref>

==Prevention==
Preventing ''Clostridium perfringens'' contamination and growth involves careful food handling, proper cooking, and appropriate storage practices. Most foods, especially beef and chicken, can be protected by cooking them to the recommended internal temperatures. Using a kitchen thermometer is the most reliable way to check that meats reach safe cooking temperatures. As a general rule, food should be avoided if it smells, tastes, looks off, or has been left out at unsafe temperatures for a long period of time.<ref name=":7">{{Cite web |last=CDC |date=2024-05-16 |title=Preventing C. perfringens Food Poisoning |url=https://www.cdc.gov/clostridium-perfringens/prevention/index.html |access-date=2024-11-21 |website=Clostridium perfringens Food Poisoning |language=en-us}}</ref>

''C. perfringens'' spores can multiply within a temperature range of 59&nbsp;°F (15&nbsp;°C) to 122&nbsp;°F (50&nbsp;°C).<ref>{{Cite journal |last1=Taormina |first1=Peter J. |last2=Dorsa |first2=Warren J. |date=2004-07-01 |title=Growth Potential of Clostridium perfringens during Cooling of Cooked Meats |url=https://www.sciencedirect.com/science/article/pii/S0362028X22036031 |journal=Journal of Food Protection |volume=67 |issue=7 |pages=1537–1547 |doi=10.4315/0362-028X-67.7.1537 |pmid=15270517 |issn=0362-028X}}</ref> To prevent bacterial growth, leftovers should be refrigerated within two hours of preparation, with their temperature chilled down to below 40&nbsp;°F (4&nbsp;°C). Large portions of food that contain meat, should be divided into smaller containers before refrigeration to ensure even cooling. Before serving leftovers, they should be reheated to at least 165&nbsp;°F (74&nbsp;°C) to destroy any bacteria that may have grown during storage.<ref name=":7" />

High-risk foods, such as canned vegetables, smoked or cured meats, and salted or smoked fish, require additional attention. Improper processing or storage can allow bacteria to grow and produce dangerous toxins. Signs of contamination, such as unusual odors, changes in texture, or bulging cans (also known as "bombage"), indicate food spoilage and should be disposed.<ref>{{Cite journal |last1=Bilska |first1=Agnieszka |last2=Wochna |first2=Krystian |last3=Habiera |first3=Małgorzata |last4=Serwańska-Leja |first4=Katarzyna |date=2024-08-18 |title=Health Hazard Associated with the Presence of Clostridium Bacteria in Food Products |journal=Foods |language=en |volume=13 |issue=16 |pages=2578 |doi=10.3390/foods13162578 |doi-access=free |issn=2304-8158 |pmc=11353352 |pmid=39200505}}</ref>

Preventing [[gas gangrene]] involves taking precautions to avoid bacterial infections. Healthcare providers follow strict protocols to prevent infections, including those caused by ''Clostridium perfringens''. To reduce the risk of gas gangrene, individuals should clean wounds thoroughly with soap and water and seek medical attention for deep or uncleanable wounds. It is also essential to monitor injuries for changes in skin condition or the onset of severe pain. Wearing protective gear when engaging in activities like biking or motorcycling can help prevent injury. Additionally, working with healthcare providers to manage underlying conditions that affect circulation or weaken the immune system can further reduce the risk of infection.<ref name=":5" />

== Treatment ==
The treatment of ''Clostridium perfringens'' infections depends on the type and severity of the condition. For severe infections, such as [[gas gangrene]] (clostridial myonecrosis), the primary approach involves surgical debridement of the affected area. This procedure removes devitalized tissue where bacteria grow, which limits the spread of the infection. [[Antimicrobial|Antimicrobial therapy]] is usually started at the same time, with penicillin being the most commonly used drug.<ref name=":8">{{Cite journal |last1=Di Bella |first1=Stefano |last2=Antonello |first2=Roberta Maria |last3=Sanson |first3=Gianfranco |last4=Maraolo |first4=Alberto Enrico |last5=Giacobbe |first5=Daniele Roberto |last6=Sepulcri |first6=Chiara |last7=Ambretti |first7=Simone |last8=Aschbacher |first8=Richard |last9=Bartolini |first9=Laura |last10=Bernardo |first10=Mariano |last11=Bielli |first11=Alessandra |last12=Busetti |first12=Marina |last13=Carcione |first13=Davide |last14=Camarlinghi |first14=Giulio |last15=Carretto |first15=Edoardo |date=June 2022 |title=Anaerobic bloodstream infections in Italy (ITANAEROBY): A 5-year retrospective nationwide survey |url=https://linkinghub.elsevier.com/retrieve/pii/S1075996422000713 |journal=Anaerobe |language=en |volume=75 |pages=102583 |doi=10.1016/j.anaerobe.2022.102583|pmid=35568274 |hdl=11368/3020691 |hdl-access=free }}</ref> However, ''C. perfringens'' shows different resistance patterns with about 20% of strains being resistant to clindamycin, and 10% being resistant to metronidazole.<ref>{{Cite journal |last1=Geremia |first1=Nicholas |last2=Sanson |first2=Gianfranco |last3=Principe |first3=Luigi |last4=Antonello |first4=Roberta Maria |last5=Zerbato |first5=Verena |last6=Luzzati |first6=Roberto |last7=Maraolo |first7=Alberto Enrico |last8=Giacobbe |first8=Daniele Roberto |last9=Sepulcri |first9=Chiara |last10=Ambretti |first10=Simone |last11=Aschbacher |first11=Richard |last12=Bartolini |first12=Laura |last13=Bernardo |first13=Mariano |last14=Bielli |first14=Alessandra |last15=Busetti |first15=Marina |date=August 2024 |title=A subanalysis of Clostridium perfringens bloodstream infections from a 5-year retrospective nationwide survey (ITANAEROBY) |url=https://linkinghub.elsevier.com/retrieve/pii/S1075996424000842 |journal=Anaerobe |language=en |volume=90 |pages=102901 |doi=10.1016/j.anaerobe.2024.102901|pmid=39214165 |url-access=subscription }}</ref> ''C. perfringens'' is often more susceptible to vancomycin when compared to other pathogenic ''Clostridia'', making it an alternative option for treatment in some cases.<ref name=":8" />

Therapies, such as [[hyperbaric oxygen therapy]] (HBOT), may also be used for severe clostridial tissue infections. HBOT increases oxygen delivery to infected tissues, creating an environment that inhibits the growth of anaerobic bacteria like ''C. perfringens''. While not commonly used, HBOT can be beneficial in certain cases.<ref>{{Cite journal |last1=Gibson |first1=A. |last2=Davis |first2=F. M. |date=1986-08-27 |title=Hyperbaric oxygen therapy in the management of Clostridium perfringens infections |url=https://pubmed.ncbi.nlm.nih.gov/3462561/ |journal=The New Zealand Medical Journal |volume=99 |issue=808 |pages=617–620 |issn=0028-8446 |pmid=3462561}}</ref>

For foodborne illness caused by ''C. perfringens'', treatment is typically unnecessary. Most people who suffer from food poisoning caused by ''C. perfringens'' usually fight off the illness without the need of any antibiotics. Extra fluids should be drank consistently until diarrhea dissipates.<ref name="cdc.gov2">{{Cite web |last=CDC |date=2023-03-24 |title=Prevent Illness From C. perfringens |url=https://www.cdc.gov/foodsafety/diseases/clostridium-perfringens.html |access-date=2023-10-01 |website=Centers for Disease Control and Prevention |language=en-us}}</ref>

== Research ==
''C. perfringens'' has shown increasing [[Multiple drug resistance|multidrug resistance]], particularly in strains from humans and animals. High resistance levels were found with antibiotics such as tetracycline, erythromycin, and sulfonamides. Genetic factors, misuse of antibiotics, and bacterial evolution are the cause of this issue. This highlights the importance of finding new treatment strategies.<ref>{{Cite journal |last1=Ba |first1=Xuli |last2=Jin |first2=Youshun |last3=Ning |first3=Xuan |last4=Gao |first4=Yidan |last5=Li |first5=Wei |last6=Li |first6=Yunhui |last7=Wang |first7=Yihan |last8=Zhou |first8=Jizhang |date=August 2024 |title=Clostridium perfringens in the Intestine: Innocent Bystander or Serious Threat? |journal=Microorganisms |language=en |volume=12 |issue=8 |pages=1610 |doi=10.3390/microorganisms12081610 |doi-access=free |issn=2076-2607 |pmc=11356505 |pmid=39203452}}</ref>

[[Multilocus sequence typing|Multilocus Sequence Typing]] (MLST) and [[Whole genome sequencing|Whole Genome Sequencing]] (WGS) have been used to find the genetic diversity of ''C. perfringens''. These methods have identified 195 distinct sequence types grouped into 25 clonal complexes from 322 genomes. Phylogenetic groups were also found in multiple different hosts and environmental sources. This highlights the bacteria's  transmission potential and adaptability across species.<ref>{{Cite journal |last1=Camargo |first1=Anny |last2=Guerrero-Araya |first2=Enzo |last3=Castañeda |first3=Sergio |last4=Vega |first4=Laura |last5=Cardenas-Alvarez |first5=María X. |last6=Rodríguez |first6=César |last7=Paredes-Sabja |first7=Daniel |last8=Ramírez |first8=Juan David |last9=Muñoz |first9=Marina |date=2022-07-22 |title=Intra-species diversity of Clostridium perfringens: A diverse genetic repertoire reveals its pathogenic potential |journal=Frontiers in Microbiology |language=English |volume=13 |doi=10.3389/fmicb.2022.952081 |doi-access=free |issn=1664-302X |pmc=9354469 |pmid=35935202}}</ref>

==References==
{{Reflist}}

==External links==
* [https://web.archive.org/web/20120301210849/http://patricbrc.org/portal/portal/patric/Taxon?cType=taxon&cId=1502 Clostridium perfringens] genomes and related information at [http://patricbrc.org/ PATRIC], a Bioinformatics Resource Center funded by [http://www.niaid.nih.gov/ NIAID]
* [https://web.archive.org/web/20130615235817/http://pathema.jcvi.org/cgi-bin/Clostridium/PathemaHomePage.cgi Pathema-''Clostridium'' Resource]
* [https://bacdive.dsmz.de/strain/2631 Type strain of ''Clostridium perfringens'' at Bac''Dive'' - the Bacterial Diversity Metadatabase]

{{Gram-positive firmicutes diseases}}
{{Toxins}}
{{Consumer Food Safety}}

{{Authority control}}
{{Taxonbar|from=Q309465}}

[[Category:Bacteria described in 1937]]
[[Category:Clostridium|perfringens]]
[[Category:Food microbiology]]
[[Category:Gas gangrene]]
[[Category:Gram-positive bacteria]]
[[Category:Medical aspects of death]]
[[Category:Pathogenic bacteria]]