Mechanisms of Drug Resistance in Mycobacterium Tuberculosis

Int J Tuberc Lung Dis. 2009 Nov;13(11):1320-30.

Abstract

The increasing emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) in the era of human immunodeficiency virus (HIV) infection presents a major threat to effective control of TB. Drug resistance in Mycobacterium tuberculosis arises from spontaneous chromosomal mutations at low frequency. Clinical drug-resistant TB largely occurs as a result of man-made selection during disease treatment of these genetic alterations through erratic drug supply, suboptimal physician prescription and poor patient adherence. Molecular mechanisms of drug resistance have been elucidated for the major first- and second-line drugs rifampicin, isoniazid, pyrazinamide, ethambutol, the aminoglycosides and the fluoroquinolones. The relationship between drug resistance in M. tuberculosis strains and their virulence/transmissibility needs to be further investigated. Understanding the mechanisms of drug resistance in M. tuberculosis would enable the development of rapid molecular diagnostic tools and furnish possible insights into new drug development for the treatment of TB.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antitubercular Agents / therapeutic use*
  • Drug Resistance, Multiple, Bacterial* / genetics
  • Extensively Drug-Resistant Tuberculosis / drug therapy*
  • Extensively Drug-Resistant Tuberculosis / microbiology
  • Extensively Drug-Resistant Tuberculosis / transmission
  • Genotype
  • Humans
  • Mutation
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / pathogenicity
  • Phenotype
  • Practice Guidelines as Topic
  • Treatment Failure
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Multidrug-Resistant / microbiology
  • Tuberculosis, Multidrug-Resistant / transmission
  • Virulence

Substances

  • Antitubercular Agents