title: The diterpenoid ent-16-kauren-19-oic acid acts as an uncoupler of the bacterial respiratory chain.
abstract: ent-16-Kauren-19-oic acid is a bacteriolytic diterpenoid present in the resin of the medicinal plant Pseudognaphalium vira vira. The compound and its methyl ester showed strong activity against gram-positive bacteria, whereas the derivative 3beta-hydroxy-ent-kauren-19-oic acid was inactive against all assayed bacteria at the maximal concentration used (250 microg/mL). The bacteriolytic effect of ent-16-kauren-19-oic acid (5 microg/mL) was confirmed with cultures of Bacillus cereus and Staphylococcus aureus, whereas the methyl derivative (12 microg/mL) showed only a bacteriostatic effect. Both compounds stimulated oxygen consumption and proton conduction of whole cells, as reflected by an abrupt increase in the extracellular pH. These results indicate that ent-16-kauren-19-oic acid acts as a respiratory chain uncoupler, and that this function is strongly affected by minor structural substitutions, suggesting a tight activity-structure relationship. The ultimate effect of the uncoupling mechanism demonstrated by ent-16-kauren-19-oic acid is bacterial lysis. The disruption of the bacterial membrane integrity caused by the diterpenoid compound was determined using SYTOX Green stain and visualized by fluorescence microscopy.
authors.affiliation: Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.
authors.forename: Janet
authors.initials: J
authors.lastname: Torres-Bustos
authors.forename: Leonardo
authors.initials: L
authors.lastname: Farías
authors.forename: Alejandro
authors.initials: A
authors.lastname: Urzúa
authors.forename: Leonora
authors.initials: L
authors.lastname: Mendoza
authors.forename: Marcela
authors.initials: M
authors.lastname: Wilkens
mesh_terms: D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D001419:Bacteria / Q000187:drug effects*; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010100:Oxygen / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D012116:Resins, Plant
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; D010936:Plant Extracts; D012116:Resins, Plant; C543983:ent-16-kauren-19-oic acid; D010100:Oxygen