mycolactone

Mycolactone is a macrolide lipid toxin produced by Mycobacterium ulcerans. It is the primary virulence factor responsible for the pathogenesis of Buruli ulcer—a necrotizing skin disease characterized by painless ulcers and massive tissue necrosis. Structurally it consists of a twelve-membered lactone ring with two polyketide side chains[1][5][9]. Mycolactone exerts pleiotropic effects including potent cytotoxicity and immunosuppression. Its main mechanism involves binding to and blocking the Sec61 translocon in the endoplasmic reticulum membrane of host cells; this inhibits co-translational translocation of secretory proteins into the ER lumen leading to their degradation via proteasome pathways[3][5][7]. This blockade results in impaired immune responses (notably T-cell activation), reduced cytokine production (e.g., TNF-alpha), apoptosis induction via mTOR inhibition[10], disruption of endothelial cell function and vascular integrity[4], as well as direct analgesic effects through targeting type II angiotensin II receptors on neurons causing hypoesthesia[2]. Mycolactone also disrupts plasma membrane lipid domains affecting cellular signaling pathways[8]. While not currently an approved pharmaceutical drug or marketed therapy itself—rather a bacterial toxin—it has been studied for its unique immunomodulatory and analgesic properties with potential therapeutic applications.

Other names

222050-77-3DTXSID10415207DTXSID-10415207DTXSID 10415207[(6S,7S,9E,12R)-12-[(E,1S,5R,6R,8R)-6,8-dihydroxy-1,3,5-trimethyl-non-3-enyl]-7,9-dimethyl-2-oxo-1-oxacyclododec-9-en-6-yl] (2E,4E,6E,8E,10E,12S,13S,15S)-12,13,15-trihydroxy-4,6 ,10-trimethyl -hexadeca -2 ,4 ,6 ,8 ,10-pentaenoate((6S ,7S ,9E ,12R ) -12-( ( E ,1 S ,5 R ,6 R ,8 R ) - 6 , 8-dihydroxy -1 , 3 , 5-trimethyl-non- 3-enyl ) - 7, 9-dimethyl- 2- oxo- 1- oxacyclododec- 9-en- 6-y l) ( 2 E, 4 E, 6 E, 8 E, 10 E, 12 S, 13 S, 15 S) - 12 , 13 , 15 - trihydroxy - 4 , 6 , 10 - trimethyl - hexadeca - ...