Clostridium spp.

  • Douglas I. Johnson


  • Genomics:
    • Clostridium botulinum A strain Hall chromosome: 3,886,916 bp; 3650 predicted ORFs (Sebaihia et al. 2007)

    • Clostridium difficile chromosome: 4,290,252 bp; 3776 predicted ORFs (Sebaihia et al. 2006)

    • Clostridium perfringens chromosome: 3,031,430 bp; 2660 predicted ORFs (Shimizu et al. 2002)

    • Clostridium septicum chromosome: 3,266,706 bp; 3125 predicted ORFs (Benamar et al. 2016)

    • Clostridium sordellii chromosome: 3,571,992 bp; 3586 predicted ORFs (Scaria et al. 2015)

    • Clostridium tetani chromosome – 2,799,250 bp; 2372 predicted ORFs (Bruggemann et al. 2003):
      • Plasmid: 74,082 bp; 61 predicted ORFs; encodes the tetanus toxin

  • Cell morphology:
    • Rod-shaped cells (Fig. 3.1)

    • Endospore formers: terminal or subterminal endospores; swollen sporangium gives cells a “drumstick” appearance

    • Flagella – most species have peritrichous flagella including C. botulinum, C. difficile, C. septicum, C. sordellii, and C. tetani:
      • C. perfringens does not have flagella.

      • The role of Clostridia flagella in virulence is unclear; may play a role in binding to host mucus.

  • Gram stain:
    • Gram positive; older cells tend to stain Gram negative

  • Growth:
    • Obligate anaerobes (vs. aerobic Bacillus spp.)

    • Ubiquitous environmental pathogens; found primarily in soil in endospore form

    • Biofilm formation (Pantaleon et al. 2014):
      • Seventy one Clostridium species can form either mono-species or multi-species biofilms.

      • Nine species have the ability to form mono-species biofilms, including the pathogens C. difficile and C. perfringens (see below).

    • At least 100 species; most are not associated with human disease:
      • Notable human pathogens: C. botulinum, C. difficile, C. perfringens, C. septicum, C. sordellii, and C. tetani


  1. Aktories K, Barth H (2004) Clostridium botulinum C2 toxin – new insights into the cellular up-take of the actin-ADP-ribosylating toxin. Int J Med Microbiol 293:557–564CrossRefPubMedGoogle Scholar
  2. Aldape MJ, Bryant AE, Stevens DL (2006) Clostridium sordellii infection: epidemiology, clinical findings, and current perspectives on diagnosis and treatment. Clin Infect Dis 43:1436–1446CrossRefPubMedGoogle Scholar
  3. Aldape MJ, Bryant AE, Ma Y, Stevens DL (2007) The leukemoid reaction in Clostridium sordellii infection: neuraminidase induction of promyelocytic cell proliferation. J Infect Dis 195:1838–1845CrossRefPubMedGoogle Scholar
  4. Alves GG, Machado de Avila RA, Chavez-Olortegui CD, Lobato FC (2014) Clostridium perfringens epsilon toxin: the third most potent bacterial toxin known. Anaerobe 30:102–107CrossRefPubMedGoogle Scholar
  5. Aronoff DM (2013) Clostridium novyi, sordellii, and tetani: mechanisms of disease. Anaerobe 24:98–101CrossRefPubMedGoogle Scholar
  6. van Asten AJ, Nikolaou GN, Grone A (2010) The occurrence of cpb2-toxigenic Clostridium perfringens and the possible role of the beta2-toxin in enteric disease of domestic animals, wild animals and humans. Vet J 183:135–140CrossRefPubMedGoogle Scholar
  7. Awad MM, Cheung JK, Tan JE, McEwan AG, Lyras D, Rood JI (2016) Functional analysis of an feoB mutant in Clostridium perfringens strain 13. Anaerobe 41:10–17CrossRefPubMedGoogle Scholar
  8. Benamar S, Cassir N, Caputo A, Cadoret F, La Scola B (2016) Complete genome sequence of Clostridium septicum strain CSUR P1044, isolated from the human gut microbiota. Genome Announcements 4Google Scholar
  9. Bruggemann H, Baumer S, Fricke WF, Wiezer A, Liesegang H, Decker I, Herzberg C, Martınez-Arias R, Merkl R, Henne A, Gottschalk G (2003) The genome sequence of Clostridium tetani, the causative agent of tetanus disease. Proc NatI Acad Sci USA 100:1316–1321CrossRefGoogle Scholar
  10. Brunt J, van Vliet AH, van den Bos F, Carter AT, Peck MW (2016) Diversity of the germination apparatus in Clostridium botulinum groups I, II, III, and IV. Front Microbiol 7:1702CrossRefPubMedPubMedCentralGoogle Scholar
  11. Chen J, Ma M, Uzal FA, McClane BA (2014) Host cell-induced signaling causes Clostridium perfringens to upregulate production of toxins important for intestinal infections. Gut Microbes 5:96–107CrossRefPubMedGoogle Scholar
  12. Chen S, Sun C, Wang H, Wang J (2015) The role of Rho GTPases in toxicity of Clostridium difficile toxins. Toxins 7:5254–5267CrossRefPubMedPubMedCentralGoogle Scholar
  13. Choo JM, Cheung JK, Wisniewski JA, Steer DL, Bulach DM, Hiscox TJ, Chakravorty A, Smith AI, Gell DA, Rood JI, Awad MM (2016) The NEAT domain-containing proteins of Clostridium perfringens bind heme. PLoS One 11:e0162981CrossRefPubMedPubMedCentralGoogle Scholar
  14. Cooksley CM, Davis IJ, Winzer K, Chan WC, Peck MW, Minton NP (2010) Regulation of neurotoxin production and sporulation by a putative agrBD signaling system in proteolytic Clostridium botulinum. Appl Environ Microbiol 76:4448–4460CrossRefPubMedPubMedCentralGoogle Scholar
  15. Ðapa T, Leuzzi R, Ng YK, Baban ST, Adamo R, Kuehne SA, Scarselli M, Minton NP, Serruto D, Unnikrishnan M (2013) Multiple factors modulate biofilm formation by the anaerobic pathogen Clostridium difficile. J Bacteriol 195:545–555CrossRefPubMedPubMedCentralGoogle Scholar
  16. Davies AH, Roberts AK, Shone CC, Acharya KR (2011) Super toxins from a super bug: structure and function of Clostridium difficile toxins. Biochem J 436:517–526CrossRefPubMedGoogle Scholar
  17. Francis MB, Allen CA, Shrestha R, Sorg JA (2013) Bile acid recognition by the Clostridium difficile germinant receptor, CspC, is important for establishing infection. PLoS Pathog 9:e1003356CrossRefPubMedPubMedCentralGoogle Scholar
  18. Freedman JC, Theoret JR, Wisniewski JA, Uzal FA, Rood JI, McClane BA (2015) Clostridium perfringens type A-E toxin plasmids. Res Microbiol 166:264–279CrossRefPubMedGoogle Scholar
  19. Gnerlich JL, Ritter JH, Kirby JP, Mazuski JE (2011) Simultaneous necrotizing soft tissue infection and colonic necrosis caused by Clostridium septicum. Surgical Infections (Larchmt) 12:501–506CrossRefGoogle Scholar
  20. Grumelli C, Verderio C, Pozzi D, Rossetto O, Montecucco C, Matteoli M (2005) Internalization and mechanism of action of clostridial toxins in neurons. Neurotoxicology 26:761–767CrossRefPubMedGoogle Scholar
  21. Hermsen JL, Schurr MJ, Kudsk KA, Faucher LD (2008) Phenotyping Clostridium septicum infection: a surgeon's infectious disease. J Surg Res 148:67–76CrossRefPubMedGoogle Scholar
  22. Hill KK, Xie G, Foley BT, Smith TJ (2015) Genetic diversity within the botulinum neurotoxin-producing bacteria and their neurotoxins. Toxicon 107:2–8CrossRefPubMedGoogle Scholar
  23. Ho TD, Ellermeier CD (2015) Ferric uptake regulator fur control of putative iron acquisition systems in Clostridium difficile. J Bacteriol 197:2930–2940CrossRefPubMedPubMedCentralGoogle Scholar
  24. Hundsberger T, Braun V, Weidmann M, Leukel P, Sauerborn M, Eichel-Streiber CV (1997) Transcription analysis of the genes tcdA-E of the pathogenicity locus of Clostridium difficile. Eur J Biochem 244:735–742CrossRefPubMedGoogle Scholar
  25. Jank T, Belyi Y, Aktories K (2015) Bacterial glycosyltransferase toxins. Cell Microbiol 17:1752–1765CrossRefPubMedGoogle Scholar
  26. Janoir C (2016) Virulence factors of Clostridium difficile and their role during infection. Anaerobe 37:13–24CrossRefPubMedGoogle Scholar
  27. Jin F, Matsushita O, Katayama S, Jin S, Matsushita C, Minami J, Okabe A (1996) Purification, characterization, and primary structure of Clostridium perfringens lambda-toxin, a thermolysin-like metalloprotease. Infect Immun 64:230–237PubMedPubMedCentralGoogle Scholar
  28. Jost BH, Billington SJ, Trinh HT, Songer JG (2006) Association of genes encoding beta2 toxin and a collagen binding protein in Clostridium perfringens isolates of porcine origin. Vet Microbiol 115:173–182CrossRefPubMedGoogle Scholar
  29. Kalb SR, Boyer AE, Barr JR (2015) Mass spectrometric detection of bacterial protein toxins and their enzymatic activity. Toxins 7:3497–3511CrossRefPubMedPubMedCentralGoogle Scholar
  30. Knapp O, Maier E, Mkaddem SB, Benz R, Bens M, Chenal A, Geny B, Vandewalle A, Popoff MR (2010) Clostridium septicum alpha-toxin forms pores and induces rapid cell necrosis. Toxicon 55:61–72CrossRefPubMedGoogle Scholar
  31. Li J, Sayeed S, Robertson S, Chen J, McClane BA (2011) Sialidases affect the host cell adherence and epsilon toxin-induced cytotoxicity of Clostridium perfringens type D strain CN3718. PLoS Pathog 7:e1002429CrossRefPubMedPubMedCentralGoogle Scholar
  32. Macha K, Giede-Jeppe A, Lucking H, Coras R, Huttner HB, Held J (2016) Ischaemic stroke and Clostridium septicum sepsis and meningitis in a patient with occult colon carcinoma – a case report and review of the literature. BMC Neurol 16:239CrossRefPubMedPubMedCentralGoogle Scholar
  33. Matsushita O, Okabe A (2001) Clostridial hydrolytic enzymes degrading extracellular components. Toxicon 39:1769–1780CrossRefPubMedGoogle Scholar
  34. Matsushita O, Yoshihara K, Katayama S, Minami J, Okabe A (1994) Purification and characterization of a Clostridium perfringens 120-kilodalton collagenase and nucleotide sequence of the corresponding gene. J Bacteriol 176:149–156CrossRefPubMedPubMedCentralGoogle Scholar
  35. Mitchell LA, Koval M (2010) Specificity of interaction between Clostridium perfringens enterotoxin and claudin-family tight junction proteins. Toxins 2:1595–1611CrossRefPubMedPubMedCentralGoogle Scholar
  36. Montecucco C, Molgo J (2005) Botulinal neurotoxins: revival of an old killer. Curr Opin Pharmacol 5:274–279CrossRefPubMedGoogle Scholar
  37. Oda M, Terao Y, Sakurai J, Nagahama M (2015) Membrane-binding mechanism of Clostridium perfringens alpha-toxin. Toxins 7:5268–5275CrossRefPubMedPubMedCentralGoogle Scholar
  38. Ohtani K, Hayashi H, Shimizu T (2002) The luxS gene is involved in cell–cell signalling for toxin production in Clostridium perfringens. Mol Microbiol 44:171–179CrossRefPubMedGoogle Scholar
  39. Pantaleon V, Bouttier S, Soavelomandroso AP, Janoir C, Candela T (2014) Biofilms of Clostridium species. Anaerobe 30:193–198CrossRefPubMedGoogle Scholar
  40. Paredes-Sabja D, Torres JA, Setlow P, Sarker MR (2008) Clostridium perfringens spore germination: characterization of germinants and their receptors. J Bacteriol 190:1190–1201CrossRefPubMedGoogle Scholar
  41. Peltier J, Courtin P, El Meouche I, Lemee L, Chapot-Chartier MP, Pons JL (2011) Clostridium difficile has an original peptidoglycan structure with a high level of N-acetylglucosamine deacetylation and mainly 3-3 cross-links. J Biol Chem 286:29053–29062CrossRefPubMedPubMedCentralGoogle Scholar
  42. Popoff MR (2011) Epsilon toxin: a fascinating pore-forming toxin. FEBS J 278:4602–4615CrossRefPubMedGoogle Scholar
  43. Popoff MR (2014) Clostridial pore-forming toxins: powerful virulence factors. Anaerobe 30:220–238CrossRefPubMedGoogle Scholar
  44. Ramirez N, Abel-Santos E (2010) Requirements for germination of Clostridium sordellii spores in vitro. J Bacteriol 192:418–425CrossRefPubMedGoogle Scholar
  45. Rood JI (1998) Virulence genes of Clostridium perfringens. Annu Rev Microbiol 52:333–360CrossRefPubMedGoogle Scholar
  46. Rupnik M, Wilcox MH, Gerding DN (2009) Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol 7:526–536CrossRefPubMedGoogle Scholar
  47. Sakurai J, Nagahama M, Hisatsune J, Katunuma N, Tsuge H (2003) Clostridium perfringens iota-toxin, ADP-ribosyltransferase: structure and mechanism of action. Adv Enzym Regul 43:361–377CrossRefGoogle Scholar
  48. Sakurai J, Nagahama M, Oda M (2004) Clostridium perfringens alpha-toxin: characterization and mode of action. J Biochem 136:569–574CrossRefPubMedGoogle Scholar
  49. Scaria J, Suzuki H, Ptak CP, Chen JW, Zhu Y, Guo XK, Chang YF (2015) Comparative genomic and phenomic analysis of Clostridium difficile and Clostridium sordellii, two related pathogens with differing host tissue preference. BMC Genomics 16:448CrossRefPubMedPubMedCentralGoogle Scholar
  50. Schropfer E, Rauthe S, Meyer T (2008) Diagnosis and misdiagnosis of necrotizing soft tissue infections: three case reports. Cases J 1:252CrossRefPubMedPubMedCentralGoogle Scholar
  51. Sebaihia M, Wren BW, Mullany P, Fairweather NF, Minton N, Stabler R, Thomson NR, Roberts AP, Cerdeno-Tarraga AM, Wang H, Holden MT, Wright A, Churcher C, Quail MA, Baker S, Bason N, Brooks K, Chillingworth T, Cronin A, Davis P, Dowd L, Fraser A, Feltwell T, Hance Z, Holroyd S, Jagels K, Moule S, Mungall K, Price C, Rabbinowitsch E, Sharp S, Simmonds M, Stevens K, Unwin L, Whithead S, Dupuy B, Dougan G, Barrell B, Parkhill J (2006) The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome. Nat Genet 38:779–786CrossRefPubMedGoogle Scholar
  52. Sebaihia M, Peck MW, Minton NP, Thomson NR, Holden MT, Mitchell WJ, Carter AT, Bentley SD, Mason DR, Crossman L, Paul CJ, Ivens A, Wells-Bennik MH, Davis IJ, Cerdeno-Tarraga AM, Churcher C, Quail MA, Chillingworth T, Feltwell T, Fraser A, Goodhead I, Hance Z, Jagels K, Larke N, Maddison M, Moule S, Mungall K, Norbertczak H, Rabbinowitsch E, Sanders M, Simmonds M, White B, Whithead S, Parkhill J (2007) Genome sequence of a proteolytic (group I) Clostridium botulinum strain Hall A and comparative analysis of the clostridial genomes. Genome Res 17:1082–1092CrossRefPubMedPubMedCentralGoogle Scholar
  53. Seddon SV, Hemingway I, Borriello SP (1990) Hydrolytic enzyme production by Clostridium difficile and its relationship to toxin production and virulence in the hamster model. J Med Microbiol 31:169–174CrossRefPubMedGoogle Scholar
  54. Seike S, Miyamoto K, Kobayashi K, Takehara M, Nagahama M (2016) Clostridium perfringens delta-toxin induces rapid cell necrosis. PLoS One 11:e0147957CrossRefPubMedPubMedCentralGoogle Scholar
  55. Shatursky O, Bayles R, Rogers M, Jost BH, Songer JG, Tweten RK (2000) Clostridium perfringens beta-toxin forms potential-dependent, cation-selective channels in lipid bilayers. Infect Immun 68:5546–5551CrossRefPubMedPubMedCentralGoogle Scholar
  56. Shimizu T, Ohtani K, Hirakawa H, Ohshima K, Yamashita A, Shiba T, Ogasawara N, Hattori M, Kuhara S, Hayashi H (2002) Complete genome sequence of Clostridium perfringens, an anaerobic flesh-eater. PNAS 99:996–1001CrossRefPubMedPubMedCentralGoogle Scholar
  57. Shukla HD, Sharma SK (2005) Clostridium botulinum: a bug with beauty and weapon. Crit Rev Microbiol 31:11–18CrossRefPubMedGoogle Scholar
  58. Sundriyal A, Roberts AK, Shone CC, Acharya KR (2009) Structural basis for substrate recognition in the enzymatic component of ADP-ribosyltransferase toxin CDTa from Clostridium difficile. J Biol Chem 284:28713–28719CrossRefPubMedPubMedCentralGoogle Scholar
  59. Swaminathan S (2011) Molecular structures and functional relationships in clostridial neurotoxins. FEBS J 278:4467–4485CrossRefPubMedGoogle Scholar
  60. Theriot CM, Young VB (2015) Interactions between the gastrointestinal microbiome and Clostridium difficile. Annu Rev Microbiol 69:445–461CrossRefPubMedPubMedCentralGoogle Scholar
  61. Tweten RK (1988a) Cloning and expression in Escherichia coli of the perfringolysin O (theta toxin) gene from Clostridium perfringens and characterization of the gene product. Infect Immun 56:3228–3234PubMedPubMedCentralGoogle Scholar
  62. Tweten RK (1988b) Nucleotide sequence of the gene for perfringolysin O (theta toxin) from Clostridium perfringens: significant homology with the genes for streptolysin O and pneumolysin. Infect Immun 56:3235–3240PubMedPubMedCentralGoogle Scholar
  63. Wilde C, Aktories K (2001) The rho-ADP-ribosylating C3 exoenzyme from Clostridium botulinum and related C3-like transferases. Toxicon 39:1647–1660CrossRefPubMedGoogle Scholar
  64. Yonogi S, Matsuda S, Kawai T, Yoda T, Harada T, Kumeda Y, Gotoh K, Hiyoshi H, Nakamura S, Kodama T, Iida T (2014) BEC, a novel enterotoxin of Clostridium perfringens found in human clinical isolates from acute gastroenteritis outbreaks. Infect Immun 82:2390–2399CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Douglas I. Johnson
    • 1
  1. 1.Department of Microbiology & Molecular GeneticsUniversity of VermontBurlingtonUSA

Personalised recommendations