Potentiation of methicillin activity against methicillin-resistant Staphylococcus aureus by diterpenes.
Totarol is a diterpene compound extracted from the totara tree. Totarol and eight other diterpenes were found to potentiate methicillin, one reducing the minimum inhibitory concentration of methicillin against resistant Staphylococcus aureus 256-fold. Totarol did not inhibit the synthesis of DNA or peptidoglycan in S. aureus, but reduced the respiration rate by 70%. Under potentiation conditions, diterpenes had only a slight effect on the respiration rate, but had a significant effect on expression of PBP 2a. We conclude that the primary staphylococcal target for totarol is the respiratory chain, but that potentiation of methicillin by diterpenes is by interference with PBP 2a expression.
Nicolson
K
K
Institute of Molecular BioSciences, Massey University, Palmerston North, New Zealand.
Evans
G
G
O'Toole
P W
PW
D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000096:biosynthesis; D004269:DNA, Bacterial / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology*; D006602:Hexosyltransferases; D008712:Methicillin / Q000494:pharmacology*; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000096:biosynthesis; D010101:Oxygen Consumption / Q000187:drug effects; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan / Q000096:biosynthesis; D010458:Peptidyl Transferases; D013211:Staphylococcus aureus / Q000187:drug effects
D001426:Bacterial Proteins; D002352:Carrier Proteins; D004269:DNA, Bacterial; D004224:Diterpenes; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D008712:Methicillin