Figures & data
Table 1. Characteristics of toxins and extracellular degradative enzymes produced by C. perfringens
Table 2. Current C. perfringens toxinotyping scheme
Table 3. C. perfringens toxinotype: disease associations
Table 4. Size and diversity C. perfringens plasmids encoding key-toxins1.
Navarro MA, McClane BA, Uzal FA. Mechanisms of action and cell death associated with Clostridium perfringens toxins. Toxins (Basel). 2018;10(5):212. Hunter SEC, Brown JE, Oynston PCF, et al. Molecular genetic analysis of beta-toxin of Clostridium perfringens reveals sequence homology with alpha-toxin, gamma-toxin, and leukocidin of Staphylococcus aureus. Infect Immun. 1993;61(9):3958–3965. Freedman JC, Shrestha A, McClane BA. Clostridium perfringens enterotoxin: action, genetics, and translational applications. Toxins (Basel). 2016;8(3):73. Cole AR, Gibert M, Popoff MR, et al. Clostridium perfringens epsilon-toxin shows structural similarity to the pore-forming toxin aerolysin. Nat Struct Mol Biol. 2004;11(8):797–798. Sakurai J, Nagahama M, Oda M, et al. Clostridium perfringens iota-toxin: structure and function. Toxins (Basel). 2009;1(2):208–228. Keyburn AL, Bannam TL, Moore RJ, et al. NetB, a pore-forming toxin from necrotic enteritis strains of Clostridium perfringens. Toxins (Basel). 2010;2(7):1913–1927. Gibert M, Jolivet-Reynaud C, Popoff MR. Beta2 toxin, a novel toxin produced by Clostridium perfringens. Gene. 1997;203(1):65–73. Manich M, Knapp O, Gibert M, et al. Clostridium perfringens delta toxin is sequence related to beta toxin, NetB, and Staphylococcus pore-forming toxins, but shows functional differences. PLoS One. 2008;3(11):e3764. Mehdizadeh Gohari I, Parreira VR, Nowell VJ, et al. A novel pore-forming toxin in type A Clostridium perfringens is associated with both fatal canine hemorrhagic gastroenteritis and fatal foal necrotizing enterocolitis. PLoS One. 2015;10(4):e0122684. Guttenberg G, Hornei S, Jank T, et al. Molecular characteristics of Clostridium perfringens TpeL toxin and consequences of mono-O-GlcNAcylation of Ras in living cells. J Biol Chem. 2012;287(30):24929–24940. Titball RW, Naylor CE, Basak AK. The Clostridium perfringens alpha-toxin. Anaerobe. 1999;5(2):51–64. Popoff MR, Bouvet P. Clostridial toxins. Future Microbiol. 2009;4(8):1021–1064. Robertson SL, Smedley JG, Singh U, et al. Compositional and stoichiometric analysis of Clostridium perfringens enterotoxin complexes in Caco-2 cells and claudin 4 fibroblast transfectants. Cell Microbiol. 2007;9(11):2734–2755. Benz R, Popoff MR. Clostridium perfringens enterotoxin. The toxin forms highly cation-selective channels in lipid bilayers. Toxins (Basel). 2018;10(9):341. Popoff MR. Clostridial pore-forming toxins: powerful virulence factors. Anaerobe. 2014;30:220–238. Keyburn AL, Boyce JD, Vaz P, et al. NetB, a new toxin that is associated with avian necrotic enteritis caused by Clostridium perfringens. PLoS Pathog. 2008;4(2):e26. Yan X, Porter CJ, Hardy SP, et al. Structural and functional analysis of the pore-forming toxin NetB from Clostridium perfringens. mBio. 2013;4(1):e00019–13. Mehdizadeh Gohari I, Brefo-Mensah EK, Palmer M, et al. Sialic acid facilitates binding and cytotoxic activity of the pore-forming Clostridium perfringens NetF toxin to host cells. PLoS One. 2018;13(11):e0206815. Rossjohn J, Feil SC, McKinstry WJ, et al. Structure of a cholesterol-binding, thiol-activated cytolysin and a model of its membrane form. Cell. 1997;89(5):685–692. Nagahama M, Ochi S, Oda M, et al. Recent insights into Clostridium perfringens beta toxin. Toxins (Basel). 2015;7(2):396–406. Yonogi S, Matsuda S, Kawai T, et al. BEC, a novel enterotoxin of Clostridium perfringens found in human clinical isolates from acute gastroenteritis outbreaks. Infect Immun. 2014;82(6):2390–2399. . Shimizu T, Ohtani K, Hirakawa H, et al. Complete genome sequence of Clostridium perfringens, an anaerobic flesh-eater. Proc Natl Acad Sci USA. 2002;99(2):996–1001. Myers GS, Rasko DA, Cheung JK, et al. Skewed genomic variability in strains of the toxigenic bacterial pathogen, Clostridium perfringens. Genome Res. 2006;16(8):1031–1040. . Mehdizadeh Gohari I, Kropinski AM, Weese SJ, et al. Plasmid characterization and chromosome analysis of two netF+ Clostridium perfringens isolates associated with foal and canine necrotizing enteritis. PLoS One. 2016;11(2):e0148344. Li J, Adams V, Bannam TL, et al. Toxin plasmids of Clostridium perfringens. Microbiol Mol Biol Rev. 2013;77(2):208–233. Watts TD, Vidor CJ, Awad MM, et al. pCP13, a representative of a new family of conjugative toxin plasmids in Clostridium perfringens. Plasmid. 2019;102:37–45. Li J, Miyamoto K, Sayeed S, et al. Organization of the cpe locus in CPE-positive Clostridium perfringens type C and D isolates. PLoS One. 2010;5(6):e10932. Revitt-Mills SA, Rood JI, Adams V. Clostridium perfringens extracellular toxins and enzymes: 20 and counting. Microbiol Aust. 2015;36(3):114–117. Freedman JC, Theoret JR, Wisniewski JA, et al. Clostridium perfringens type A-E toxin plasmids. Res Microbiol. 2015;166(4):264–279. Ma M, Li J, McClane BA. Genotypic and phenotypic characterization of Clostridium perfringens isolates from Darmbrand cases in post-World War II Germany. Infect Immun. 2012;80(12):4354–4363. Sayeed S, Li J, McClane BA. Characterization of virulence plasmid diversity among Clostridium perfringens type B isolates. Infect Immun. 2010;78(1):495–504. Gurjar A, Li J, McClane BA. Characterization of toxin plasmids in Clostridium perfringens type C isolates. Infect Immun. 2010;78(11):4860–4869. Adams V, Li J, Wiosniewski JA, et al. Virulence plasmids of spore-forming bacteria. Microbiol Spectr. 2014;2(6):10.1128. Sayeed S, Li J, McClane BA. Virulence plasmid diversity in Clostridium perfringens type D isolates. Infect Immun. 2007;75(5):2391–2398. Miyamoto K, Li J, Sayeed S, et al. Sequencing and diversity analyses reveal extensive similarities between some epsilon-toxin-encoding plasmids and the pCPF5603 Clostridium perfringens enterotoxin plasmid. J Bacteriol. 2008;190(21):7178–7188. Li J, Miyamoto K, McClane BA. Comparison of virulence plasmids among Clostridium perfringens type E isolates. Infect Immun. 2007;75(4):1811–1819. Miyamoto K, Yumine N, Mimura K, et al. Identification of novel Clostridium perfringens type E strains that carry an iota toxin plasmid with a functional enterotoxin gene. PLoS One. 2011;6(5):e20376. Miyamoto K, Fisher DJ, Li J, et al. Complete sequencing and diversity analysis of the enterotoxin-encoding plasmids in Clostridium perfringens type A non-food-borne human gastrointestinal disease isolates. J Bacteriol. 2006;188(4):1585–1598. Fisher DJ, Miyamoto K, Harrison B, et al. Association of beta2 toxin production with Clostridium perfringens type A human gastrointestinal disease isolates carrying a plasmid enterotoxin gene. Mol Microbiol. 2005;56(3):747–762. Nowell VJ, Kropinski AM, Songer JG, et al. Genome sequencing and analysis of a type A Clostridium perfringens isolate from a case of bovine clostridial abomasitis. PLoS One. 2012;7(3):e32271. Parreira VR, Costa M, Eikmeyer F, et al. Sequence of two plasmids from Clostridium perfringens chicken necrotic enteritis isolates and comparison with C. perfringens conjugative plasmids. PLoS One. 2012;7(11):e49753. Bannam T, Yan X, Harrison P, et al. Necrotic enteritis-derived Clostridium perfringens strain with three closely related independently conjugative toxin and antibiotic plasmids. mBio. 2011;2(5):e00190–11. Lacey JA, Allnutt TR, Vezina B, et al. Whole genome analysis reveals the diversity and evolutionary relationships between necrotic enteritis-causing strains of Clostridium perfringens. BMC Genomics. 2018;19(1):379. Mehdizadeh Gohari I, Kropinski AM, Weese SJ, et al. NetF-producing Clostridium perfringens: clonality and plasmid pathogenicity loci analysis. Infect Genet Evol. 2017;49:32–38. Li J, McClane BA. Evidence that VirS is a receptor for the signaling peptide of Clostridium perfringens agr-like quorum sensing system. mBio. 2020;11(5):e02219–20. Ohtani K, Shimizu T. Regulation of toxin production in Clostridium perfringens. Toxins (Basel). 2016;8(7):207.