Molecular mechanisms of drug resistance in Mycobacterium tuberculosis

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

In spite of forty years of effective chemotherapy for tuberculosis, the molecular mechanisms of antibacterial compounds in Mycobacterium tuberculosis have only recently been revealed. Broad spectrum antibacterials, including streptomycin, rifampicin, and fluoroquinolones have been demonstrated to act on the same targets in M. tuberculosis as they do in E. coli. Resistance to these agents results from single mutagenic events that lead to amino acid substitutions in their target proteins. The mechanisms of action of the unique antitubercular drugs, including isoniazid, ethambutol, and pyrazinamide have also recently been defined. Resistance to isoniazid can be caused either by mutations in the katG-encoded catalase-peroxidase, the enzyme responsible for drug activation, or by the molecular target, the inhA- encoded long chain enoyl-ACP reductase. Ethambutol appears to block specifically the biosynthesis of the arabinogalactan component of the mycobacterial cell envelope, and pyrazinamide has no known target. With the resurgence of tuberculosis and the appearance of strains which are multiply resistant to the above compounds, present tuberculosis chemotherapies are threatened. New approaches to the treatment of multi drug-resistant tuberculosis are needed.

Original languageEnglish (US)
Pages (from-to)215-239
Number of pages25
JournalAnnual Review of Biochemistry
Volume65
StatePublished - 1996

Fingerprint

Pyrazinamide
Ethambutol
Chemotherapy
Isoniazid
Mycobacterium tuberculosis
Drug Resistance
Tuberculosis
Antitubercular Agents
Biosynthesis
Fluoroquinolones
Streptomycin
Rifampin
Pharmaceutical Preparations
Catalase
Escherichia coli
Peroxidase
Drug Therapy
Multidrug-Resistant Tuberculosis
Oxidoreductases
Substitution reactions

Keywords

  • antibacterial
  • drug action
  • drug resistance
  • tuberculosis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular mechanisms of drug resistance in Mycobacterium tuberculosis. / Blanchard, John S.

In: Annual Review of Biochemistry, Vol. 65, 1996, p. 215-239.

Research output: Contribution to journalArticle

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