Parrish M, Bishai WR, Heine HS, Kuhajda FP, Dick JD; American Society for Microbiology. General Meeting.
Abstr Gen Meet Am Soc Microbiol. 1997 May 4-8; 97: 567 (abstract no. U134).
Johns Hopkins Medical Institutions, Baltimore, MD.
Cerulenin is an antibiotic and potent inhibitor of fatty acid synthase systems in a variety of prokaryotic and eukaryotic cells. Using the Bactec radiometric growth system, we have observed that cerulenin inhibits the growth of Mycobacterium smegmatis, M. bovis BCG, and M. avium-intracellulare. All species tested were susceptible to cerulenin with MIC's ranging from 1.5 to 6.25 micrograms/ml. A 2-dimensional thin-layer chromatography system was used to examine individual lipid classes in the presence of a subinhibitory concentration of cerulenin in all three species of mycobacteria. Qualitative and quantitative effects of cerulenin on the synthesis of free unesterified fatty acids, triglycerides, phospholipids, glycolipids, glycopeptidolipids and mycolic acids were examined. Quantitatively, long chain extractable lipids were absent with cerulenin treatment in M. Smegmatis and were significantly decreased in both M. bovis BCG and M. avium-intracellulare. Qualitative changes in several of these lipid classes indicates inhibition in the synthesis of intermediate and long chain fatty acids with chain lengths greater than 24 carbons. Our results suggest, in the three mycobacterial species tested, cerulenin's primary inhibitory effect may be in intermediate and long chain lipid synthesis, with little effect on the synthesis of other lipid classes. Since pathogenic mycobacteria produce novel long chain fatty chains, inhibition of fatty acid synthesis offers a potential target for the development of antimycobacterial agents.
Publication Types:
Keywords:
- Anti-Bacterial Agents
- BCG Vaccine
- Cerulenin
- Fatty Acid Synthetase Complex
- Fatty Acids
- Lipids
- Microbial Sensitivity Tests
- Mycobacterium
- Mycobacterium Infections
- Mycobacterium bovis
- Mycobacterium smegmatis
- Mycolic Acids
- Phospholipids
Other ID:
UI: 102235525
From Meeting Abstracts