PubMed · 7970976
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
N Abughali, F Van der Kuyp, W Annable, M L Kumar. 1994. Congenital tuberculosis.. https://doi.org/10.1097/00006454-199408000-00012
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
The molecular revolution is beginning to have an impact on all aspects of tuberculosis. Work in diagnostics is expected to progress in maximizing genetic testing of mycobacteria. Drug development will benefit from recently acquired knowledge on molecular mechanisms of drug action. The availability of the complete genome of Mycobacterium tuberculosis, and better tools for genetic work with mycobacteria, will promote the development of vaccine candidates. Our work has contributed to the definition of the mechanisms of resistance to rifampin, fluoroquinolones, and ethambutol, and, using molecular analysis, to a better understanding of the epidemiology of mycobacterial infections. This overview of the direction of tuberculosis research today illustrates the impact of novel scientific approaches on the investigation of old problems.
The preferred antitubercular drug isoniazid specifically targets a long-chain enoyl-acyl carrier protein reductase (InhA), an enzyme essential for mycolic acid biosynthesis in Mycobacterium tuberculosis. Despite the widespread use of this drug for more than 40 years, its precise mode of action has remained obscure. Data from x-ray crystallography and mass spectrometry reveal that the mechanism of isoniazid action against InhA is covalent attachment of the activated form of the drug to the nicotinamide ring of nicotinamide adenine dinucleotide bound within the active site of InhA.
The crude methanol extract of the Kenyan shrub Leucas volkensii Gürke (Labiatae) displayed in a radiorespirometric bioassay antimycobacterial activity against Mycobacterium tuberculosis. Bioassay-guided fractionation of the crude extract led to the identification of (E)-phytol as the principal active component with a minimum inhibitory concentration (MIC) of 2 micrograms/ml, a value also observed for (3R,S,7R,11R)-phytanol, (Z)-phytol, and a commercially available 2:1 mixture of (E)- and (Z)-phytol. The derivatives (E)-phytol acetate, a mixture of the (2S,3S)- and (2R,3R)-isomers of (E)-phytol epoxide and (3R,S,7R,11R)-phytanic acid displayed lower activities with MICs of 8, 16, and > 128 micrograms/ml, respectively. Geraniol and farnesol, displayed MICs of 64 and 8 micrograms/ml, respectively. The activities of (E)-phytol, (Z)-phytol and (3R,S,7R,11R)-phytanol were found to be in the same range as ethambutol, a clinically useful drug with an MIC in the range 0.95-3.8 micrograms/ml.