The diterpenoid ent-16-kauren-19-oic acid acts as an uncoupler of the bacterial respiratory chain.
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.
Torres-Bustos
Janet
J
Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.
Farías
Leonardo
L
Urzúa
Alejandro
A
Mendoza
Leonora
L
Wilkens
Marcela
M
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
D000900:Anti-Bacterial Agents; D004224:Diterpenes; D010936:Plant Extracts; D012116:Resins, Plant; C543983:ent-16-kauren-19-oic acid; D010100:Oxygen