Gliotoxin

Gliotoxin is a sulfur-containing antibiotic produced by some unrelated species of pathogenic fungi, such as Aspergillus, Trichoderma, and Penicillium, and by the yeast Candida. It was originally isolated from Gliocladium fimbriatum, and was named accordingly. It is an epipolythiodioxopiperazine metabilite.

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Gliotoxin possesses immunosuppressive properties as it may suppress and cause apoptosis in certain types of cells of the immune system, including neutrophils, eosinophils, and granulocytes. Causes apoptosis in macrophages and thymocytes. It also acts as an inhibitor of farnesyl transferase. It noncompetitively inhibits the chymotrypsin-like activity of the 20S proteasome. In vivo it displays anti-inflammatory activity.^[1] It acts by blocking thiol groups in the cell membranes.

References

1. ^ [1]

• Identification of an agent in cultures of Aspergillus fumigatus displaying anti-phagocytic and immunomodulating activity in vitro: A. Müllbacher, et al.; J. Gen. Microbiol. 131, 1251 (1985)

• "Mechanism of gliotoxin action and factors mediating gliotoxin sensitivity". R.W. Jones & J.G. Hancock; J. Gen. Microbiol. 134: 2067-2075 (1988)

• Gliotoxin stimulates Ca²⁺ release from intact rat liver mitochondria: M. Schweizer & C. Richter; Biochemistry 33, 13401 (1994)
• Extracellular calcium is not required for gliotoxin or dexamethasone- induced DNA fragmentation: a reappraisal of the use of EGTA: P. Waring & A. Sjaarda; Int. J. Immunopharmacol. 17, 403 (1995)