MAKI H, MIURA K, YAMANO Y, SHIMADA J, KUWAHARA S; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 329 (abstract no. 1273).
Discov. Res. Labs., Shionogi & Co. Ltd., Toyonaka, JAPAN
Katanosin B and plusbacin A3 are naturally occurring cyclic depsipeptide antibiotics, which are active against methicillin-resistant Staphylococcus aureus and VanA-type vancomycin-resistant enterococci with MIC ranging from 0.39 to 1.56 microg/ml. Both antibitics have been reported to be inhibitors of cell wall synthesis on the basis of their inhibiting the incorporation of radio-labeled diaminopimelic acid into the cell wall peptidoglycan of bacilli. In the present study, the mechanism of action was further elucidated with using the target organism and vancomycin as a comparator. Both antibiotics were examined for effects on peptidoglycan biosynthesis, using the particulate enzymes prepared from S. aureus SRM133, a laboratory mutant with enhanced activity of peptidoglycan formation. The effects on accumulation of lipid intermediate and of nascent peptidoglycan were examined by incorporation of radio-labeled substrates detected on thin layer chromatography. Both antibiotics inhibited the formation of nascent peptidoglycan at several times lower concentrations than that of vancomycin. Both antibiotics also inhibited the formation of lipid intermediate, although needed a few times higher concentrations compared to transglycosylation inhibition. While the accumulation of lipid intermediates was not curtailed by excess of vancomycin, as noted in literature. The antibacterial activity of both antibiotics against vancomycin-resistant enterococci might be explained by blocking transglycosylation and its foregoing steps of cell wall synthesis.
Publication Types:
Keywords:
- Anti-Bacterial Agents
- Cell Wall
- Depsipeptides
- Enterococcus
- Microbial Sensitivity Tests
- Peptidoglycan
- Staphylococcus aureus
- Vancomycin
- Vancomycin Resistance
- chemical synthesis
- immunology
- katanosin B
- plusbacin A3
Other ID:
UI: 102246652
From Meeting Abstracts