Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium

@article{Mdluli1998MechanismsII,
  title={Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium},
  author={Khisimuzi E. Mdluli and John Swanson and Elizabeth R. Fischer and Richard E. Lee and Clifton E. Barry, III},
  journal={Molecular Microbiology},
  year={1998},
  volume={27}
}
Isoniazid (INH), which acts by inhibiting mycolic acid biosynthesis, is very potent against the tuberculous mycobacteria. It is about 100‐fold less effective against Mycobacterium avium. This difference has often been attributed to a decreased permeability of the cell wall. We measured the rate of conversion of radiolabelled INH to 4‐pyridylmethanol by whole cells and cell‐free extracts and estimated the permeability barrier imposed by the cell wall to INH influx in Mycobacterium tuberculosis… Expand
Mechanisms of isoniazid resistance in Mycobacterium tuberculosis.
  • C. Barry, R. Slayden, K. Mdluli
  • Biology, Medicine
  • Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy
  • 1998
TLDR
Resistance to INH develops primarily through failure to activate the prodrug due to point mutations in the katG gene, and several other loci, such as the alkylhydroperoxidase AhpC and the enoylreductase InhA, may contribute to InH resistance. Expand
Colistin as a potentiator of anti-TB drug activity against Mycobacterium tuberculosis.
TLDR
This is the first study showing that colistin potentiates the activity of isoniazid and amikacin against M. tuberculosis and prevents the emergence of resistance to anti-TB drugs. Expand
Mechanisms of Action and Resistance of the Antimycobacterial Agents
This chapter will review the mechanisms of action and resistance of the antimycobacterial agents, with an emphasis on the four first-line antituberculosis drugs isoniazid, rifampin, pyrazinamide, andExpand
Genes Required for Intrinsic Multidrug Resistance in Mycobacterium avium
TLDR
Ma2520 and pks12 are the first genes to be linked by mutation to intrinsic drug resistance in MAC, which appears to have different genetic mechanisms for resisting the effects of these antibiotics. Expand
Resistant mutants of Mycobacterium tuberculosis selected in vitro do not reflect the in vivo mechanism of isoniazid resistance
TLDR
It is concluded that the high in vitro mutation rate for isoniaZid resistance is not a satisfactory explanation for the fact that isoniazid monoresistance is significantly more widespread than monores resistance to rifampicin. Expand
A mutant of Mycobacterium smegmatis defective in the biosynthesis of mycolic acids accumulates meromycolates.
  • J. Liu, H. Nikaido
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1999
TLDR
This work has isolated a mycolate-deficient mutant strain of Mycobacterium smegmatis mc2-155 by chemical mutagenesis followed by screening for increased sensitivity to novobiocin and found that this mutant was hypersensitive to other hydrophobic compounds such as crystal violet, rifampicin, and erythromycin. Expand
In vitro synergic effect of beta-lapachone and isoniazid on the growth of Mycobacterium fortuitum and Mycobacterium smegmatis.
TLDR
In combination, these two drugs had a bactericidal effect and sterilised both cultures in 96 h and these results are valuable because antibiotic-resistant bacteria are a major public health problem. Expand
Isoniazid affects multiple components of the type II fatty acid synthase system of Mycobacterium tuberculosis
TLDR
The results suggest that these components of the FAS II complex are not independently regulated and that alterations in the expression level of InhA affect expression levels of KasA, which appears to be tightly correlated with INH sensitivity. Expand
Inactivation of the antigen 85C gene profoundly affects the mycolate content and alters the permeability of the Mycobacterium tuberculosis cell envelope
TLDR
Data demonstrate that: (i) antigen 85C is involved directly or indirectly in the transfer of mycolates onto the cell wall of the whole bacterium; (ii) the enzyme is not specific for a given type of my colate; and (iii) the cellwall‐linked mycolate layer may represent a barrier for the diffusion of small hydrophobic and hydrophilic molecules. Expand
Isoniazid accumulation in Mycobacterium smegmatis is modulated by proton motive force-driven and ATP-dependent extrusion systems.
TLDR
It is demonstrated that INH accumulation in Mycobacterium smegmatis is enhanced both upon addition of both a proton motive force (pmf) uncoupler, carbonylcyanide m-chlorophenylhydrazone (CCCP), and upon additionof ortho-vanadate, an inhibitor of ATP-dependent efflux pumps. Expand
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Results suggest that InhA is likely a primary target of action for INH and ETH and that it may be involved in mycolic acid biosynthesis. Expand
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TLDR
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