When an actively growing culture of the H37Ra strain of Mycobacterium tuberculosis was exposed to isoniazid at a concentration of 0.5 mug/ml, the cells began to lose their ability to synthesize mycolic acids immediately. After 60 min, the cells had completely lost this ability. The synthesis of the three mycolate components-alpha-mycolate, methoxymycolate, and beta-mycolate-was inhibited. The viability of the isoniazid-treated cells was unaffected up to about 60 min of exposure, after which time there was a gradual decline in the viability to about 18% after 180 min. Correspondingly, growth of the drug-treated cells slowed down and stopped after 24 hr. The inhibition of the synthesis of mycolic acids was reversible if the drug was removed before the loss of viability set in. Incubation of the viable cells in the absence of the drug for 24 hr restored the mycolate synthesis. These results strongly suggest that the inhibition of the synthesis of the mycolic acids is closely associated with the primary mechanism of action of isoniazid on the tubercle bacilli. The sequence of events which leads to the loss of viability of cells exposed to isoniazid is described.
The lipids of Mycobacterium tuberculosis BCG: fractionation, composition, turnover and the effects of isoniazid
A fast and efficient metal-mediated oxidation of isoniazid and identification of isoniazid-NAD(H) adducts
Isonicotinic acid hydrazide induced changes and inhibition in mycolic acid synthesis in Nocardia and related taxa
Isolation and characterization of the monounsaturated long chain fatty acids of Mycobacterium tuberculosis
Overproduction of mycobacterial ribosomal protein S13 induces catalase/peroxidase activity and hypersensitivity to isoniazid in Mycobacterium smegmatis
Cloning, sequencing and characterization of a fatty acid synthase-encoding gene from Mycobacterium tuberculosis var. bovis BCG
Mode of action of antituberculous drugs and mechanisms of drug resistance in Mycobacterium tuberculosis
Design, synthesis, molecular docking and 3D-QSAR studies of potent inhibitors of enoyl-acyl carrier protein reductase as potential antimycobacterial agents
Susceptibility of Mycobacterium tuberculosis to isoniazid and its derivative, 1-isonicotinyl-2-nonanoyl hydrazine: investigation at cellular level
Structural investigation of mutant Mycobacterium smegmatis arylamine N-acetyltransferase: a model for a naturally occurring functional polymorphism in Mycobacterium tuberculosis arylamine N-acetyltransferase
Design, synthesis, and X-ray analysis of a glycoconjugate bound to Mycobacterium tuberculosis antigen 85C
Novel 1,2,3-triazole derivatives for use against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain
Arylamine N-acetyltransferase of Mycobacterium tuberculosis is a polymorphic enzyme and a site of isoniazid metabolism
Targeted replacement of the mycocerosic acid synthase gene in Mycobacterium bovis BCG produces a mutant that lacks mycosides
Characterization of 7-amino-4-methylcoumarin as an effective antitubercular agent: structure-activity relationships
Precise null deletion mutations of the mycothiol synthesis genes reveal their role in isoniazid and ethionamide resistance in Mycobacterium smegmatis.
Mycobacterium tuberculosis dihydrofolate reductase is not a target relevant to the antitubercular activity of isoniazid.
SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis.
Antigen 85C inhibition restricts Mycobacterium tuberculosis growth through disruption of cord factor biosynthesis.
Specificity of isoniazid on growth inhibition and competition for an oxidized nicotinamide adenine dinucleotide regulatory site on the electron transport pathway in Mycobacterium phlei.
Differentiation of catalases in Mycobacterium phlei on the basis of susceptibility to isoniazid: association with peroxidase and acquired resistance to isoniazid.
Isoniazid inhibition of the synthesis of monounsaturated long-chain fatty acids in Mycobacterium tuberculosis H37Ra.
Relationship between the uptake of isoniazid and its action on in vivo mycolic acid synthesis in Mycobacterium tuberculosis.
Isoniazid inhibition of mycolic acid synthesis by cell extracts of sensitive and resistant strains of Mycobacterium aurum.
Scanning electron microscopy of the H37Ra strain of Mycobacterium tuberculosis exposed to isoniazid.
Isoniazid activation defects in recombinant Mycobacterium tuberculosis catalase-peroxidase (KatG) mutants evident in InhA inhibitor production.
Upregulation of the phthiocerol dimycocerosate biosynthetic pathway by rifampin-resistant, rpoB mutant Mycobacterium tuberculosis.
AccD6, a member of the Fas II locus, is a functional carboxyltransferase subunit of the acyl-coenzyme A carboxylase in Mycobacterium tuberculosis
Inactivation of the inhA-encoded fatty acid synthase II (FASII) enoyl-acyl carrier protein reductase induces accumulation of the FASI end products and cell lysis of Mycobacterium smegmatis.
Characterization of the Mycobacterium tuberculosis iniBAC promoter, a promoter that responds to cell wall biosynthesis inhibition.
CRISPR Screens in Drug Resistance
CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.