Alpha-toxin

The alpha-toxin is characterised as lethal and necrotizing.^{[citation needed]}

The type A alpha-toxin is oedematising.^[9] It acts by causing morphological changes to all cell types especially endothelial cells by inhibition of signal transduction pathways,^[10] resulting in the breakdown of cytoskeletal structures.^[11] 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 5 ng/ml (5 parts per billion) with 50% of cells rounded at 50 ng/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.^[12] Alpha-toxins are glycosyltransferases, modifying and thereby inactivating different members of the Rho and Ras subfamily of small GTP-binding proteins.^[13][14][15] C novyi type A alpha-toxin is unique in using UDP-N-acetylglucosamine rather than UDP-glucose as a substrate.^[16]

Beta-toxin

The beta-toxin is characterised as haemolytic, necrotizing lecithinase.^{[citation needed]}

Gamma-toxin

The gamma-toxin is characterised as haemolytic, lecithinase.^{[citation needed]}

Delta-toxin

The delta-toxin is characterised as oxygen labile haemolysin.^{[citation needed]}

Epsilon-toxin

The epsilon-toxin is characterised as lecithino-vitelin^{[check spelling]} and thought to be responsible for the pearly layer found in cultures.

Zeta-toxin

The zeta-toxin is characterised as haemolysin.^{[citation needed]}

Tissue penetration

Wound infection by C novyi and many other clostridium species cause gas gangrene^[17] Spontaneous infection is mostly associated with predisposing factors of hematologic or colorectal malignancies and with diabetes mellitus,^[18] although Gram-negative organisms, including Escherichia coli, may lead to a gas gangrene-like syndrome in diabetic patients. This presents with cellulitis and crepitus, and may be mistaken for gas gangrene.^[19] Spontaneous, nontraumatic, or intrinsic infections from a bowel source have been increasingly reported recently.^[20]

Clostridium novyi has been implicated in mortality among injecting illegal drug users.^[21][22]

Epithelial infections

Symptoms are often non-specific including, colitis^{[citation needed]}, oedematous duodenitis^{[citation needed]}, and fever with somnolence^{[citation needed]}.

Testing is problematical with figures presented by McLauchlin and Brazier [cited above] suggesting a false negative rate of about 40% under ideal conditions. Only positive results may be regarded as reliable. In the absence of a positive test, C. novyi type A may be inferred from characterisation by clinical observation, table 2.

Chronic infection leading to leaky capillaries may also cause retinal haemorrhages and oedema in the lower extremities leading to necrosis and gangrene. Leaky nephrons may compromise the ability of kidneys to concentrate urine leading to frequent urination and dehydration.^{[citation needed]}