User:AFB396/Clostridium novyi

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Clostridium novyi

Clostridium novyi (oedematiens) a

toxins they produce. Some authors include Clostidium haemolyticum as Clostidium novyi type D. C novyi is closely related to Clostridium botulinum types C and D as Yoshimasa Sasaki et al have demonstrated by 16S rDNA sequence analysis.[1] The PAGE analysis reported in ref 1 seems to indicate that the differences between these closely related types is a matter of gene
expression rather than major genetic differences. For example type C can be induced to produce the lethal alpha-toxin.
Isolating and identifying C novyi is difficult due to its extreme anaerobic nature. Commercial kits may not be adequate.[2]
It is also fastidious and difficult to culture, requiring the presence of
thiols.[3]

Toxins

The toxins are designated by Greek letters. The toxins normally produced by the various types are shown in table 1[4]
Table 1
C novyi type Toxins
A alpha, gamma, delta, epsilon
B alpha, beta, zeta
C gamma

The alpha-toxin of Clostridium botulinum types C and D, is similar to the C novyi beta-toxin. The A and B toxins of Clostridium difficile show homology with the alpha-toxin of C novyi as does the lethal toxin of clostridium sordellii.[5]

Alpha toxin

The alpha-toxin is characterised as lethal and

necrotizing
.
The type A alpha-toxin is oedematous.[6] It acts by causing morphological changes to endothelial cells by inhibition of signal transduction pathways [7], resulting in the breakdown of cytoskeletal structures.[8] The cells of the microvascular system become spherical and the attachments to neighbouring cells are reduced to thin strings. This results in leakage from the capillaries leading to oedema. The threshold concentration for this action to occur is 5ng/ml with 50% of cells rounded at 50ng/ml.

The duodenum is particularly sensitive to the toxin. Injection into dogs resulted in extreme oedema of the submucosal tissues of the duodenum while leaving the stomach uninjured. Injection into the eye resulted in lesions similar to flame haemorrhages found in diabetic retinopathy[9].


:The toxin is a large 250-kDa protein the active part of which is the NH2-terminal 551 amino-acid fragment.[10] Alpha-toxins are glycosyltransferases, modifying and thereby inactivating different members of the Rho and Ras subfamily of small GTP-binding proteins[11][12][13] C novyi type A alpha-toxin is unique in using UDP-N-acetylglucosamine rather than UDP-glucose as a substrate. [14]

Beta-Toxin

The beta-toxin is characterised as haemolytic, necrotizing lecithinase.

Gamma-Toxin

The gamma-toxin is characterised as haemolytic, lecithinase.

Delta-Toxin

The delta-toxin is characterised as oxygen labile haemolysin.

Epsilon-Toxin

The epsilon-toxin is characterised as lecithino-vitelin and thought to be responsible for the pearly layer found in cultures.

Zeta-Toxin

The zeta-toxin is characterised as haemolysin.

Human diseases

The type and severity of the disease caused depend on penetration of the tissues. The epithelium of the alimentary tract generally provides an effective barrier to penetration.
Wound infection causes gas gangrene[15]
C novyi has been implicated in mortality among injecting illegal drug users. [16][17]

Animal diseases

Gas gangrene

References

  1. ^ Yoshimasa Sasaki et al:Phylogenetic positions of Clostridium novyi and Clostridium haemolyticum based on 16S rDNA sequences; International Journal of Systematic and Evolutionary Microbiology (2001), 51, 901–904.
  2. ^ http://jmm.sgmjournals.org/cgi/reprint/51/11/985.pdf Brazier J.S. et al: Isolation and identification of Clostridium spp.from infections associated with the injection of drugs: experiences of a microbiological investigation team. J. Med. Microbiol. — Vol. 51 (2002), 985–989
  3. ^ http://mic.sgmjournals.org/cgi/reprint/53/3/415 Moore W.B.: Solidified Media Suitable for the Cultivation of Clostridium novyi Type B. J. gen. Microbiol. (1968), 53, 415-423
  4. ^ http://mic.sgmjournals.org/cgi/content/abstract/1/1/91 Oakley c.l. et al:The toxins of Clostridium oedematiens (Cl. novyi):Journal of General Microbiology 1 (1947), 91-107
  5. ^ Hofmann F. et al 1995 Sequencing and analysis of the gene encoding the alpha-toxin of Clostridium novyi proves its homology to toxiins A and B of Clostridium difficile. Mol Gen Genet 247:670-679
  6. ^ http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=313478 Brette P. et al:Pharmacological and Biochemical Studies of Cytotoxicity of Clostridium novyi Type A Alpha-Toxin: Infection and Immunity August 1989 p2507-2513
  7. ^ http://www.jbc.org/cgi/reprint/270/23/13932 Schmidt M et al.: Inhibition of receptor signalling to phospholipase D by Clostridium difficile toxin B—role of Rho proteins. J Biol Chem. 1996;271:2422–2426.
  8. ^ http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=257268&blobtype=pdf Müller H. et al: Morphological changes of cultured endothelial cells after microinjection of toxins that act on the cytoskeleton. Infect Immun. 1992;60:3007–3010.
  9. ^ http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=313478 Aub J.C. et al:PHYSIOLIC ACTION OF CLOSTRIDIUM OEDEMATIENS (NOVYI) IN DOGS
  10. ^ http://iai.asm.org/cgi/reprint/68/11/6378.pdf Busch C. et al:Characterisation of the Catalytic Domain of Clostridium novyi Alpha Toxin: Infection and Immunity November 2000 p6378-6383
  11. ^ http://www.jbc.org/cgi/content/abstract/271/17/10149 Just I. et al: Inactivation of Ras by Clostridium sordellii lethal toxin-catalyzed glucosylation. J Biol Chem. 1996;271:10149–10153.
  12. ^ Just I. et al: Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature. 1995;375:500–503.
  13. ^ http://www.jbc.org/cgi/reprint/270/23/13932 Just I.etal: The enterotoxin from Clostridium difficile (ToxA) monoglucosylates the Rho proteins. J Biol Chem. 1995;270:13932–13936.
  14. ^ http://www.jbc.org/cgi/reprint/271/41/25173 Selzer J.et al: Clostridium novyi alpha-toxin-catalyzed incorporation of GlcNAc into Rho subfamily proteins. J Biol Chem. 1996;271:25173–25177.
  15. ^ http://iai.asm.org/cgi/reprint/68/11/6378.pdf Hatheway C. L. 1990 Toxigenic Clostridia. Clon Microbiol Rev 366-98
  16. ^ http://arpa.allenpress.com/pdfserv/10.1043%2F1543-2165(2003)127%3C1465:AFIAOO%3E2.0.CO%3B2 Finn S.P. et al: Autopsy Findings in an Outbreak of Severe Systemic Illness in Heroin Users Following Injection Site Inflammation: An Effect of Clostridium novyi Exotoxin? Archives of Pathology and Laboratory Medicine: Vol. 127, No. 11, pp. 1465–1470.
  17. ^ http://jmm.sgmjournals.org/cgi/content/full/51/11/990 McLauchlin J. et al: Amplified fragment length polymorphism (AFLP) analysis of Clostridium novyi, C. perfringens and Bacillus cereus isolated from injecting drug users during 2000. J. Med. Microbiol. -- Vol. 51 (2002), 990-1000




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