Estimation of efflux mediated multi-drug resistance and its correlation with expression levels of two major efflux pumps in mycobacteria

J Commun Dis. 2006 Mar;38(3):246-54.


Multidrug resistance has been posing an increasing problem in the treatment of tuberculosis. Mutations in the genomic targets of drugs have been identified as the major mechanism behind this resistance. However, high degree of resistance in some isolates towards major drugs like rifampicin, isoniazid, ethambutol and streptomycin can not be explained solely on the basis of mutations. Besides this, certain other mechanisms like efflux pumps have also been considered as alternative mechanisms in the drug resistant isolates where there is no mutation and these mechanisms are specially important for drug resistance in non-tuberculous mycobacteria (NTM). In this study, we have estimated efflux pump mediated drug resistance in different mycobacterial species with the help of efflux pump inhibitors. All major anti-tuberculous drugs have been shown to be extruded by efflux pumps and the degree to which these drugs are extruded, vary in different mycobacterial species and isolates. The correlation of this resistance with functional activity of two major efflux pump genes pstB and Rv1258c was also assessed by reverse transcription PCR. Besides the significant role of these pumps observed, other efflux pumps, present in mycobacteria, may also be involved in drug resistance and need to be investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / drug effects*
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Adenosine Triphosphatases / drug effects*
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Bacterial Proteins / drug effects*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Drug Resistance, Multiple, Bacterial / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Multidrug Resistance-Associated Proteins / drug effects*
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism
  • Mycobacterium phlei / drug effects*
  • Mycobacterium phlei / genetics
  • Mycobacterium phlei / physiology
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics
  • Nontuberculous Mycobacteria / drug effects*
  • Nontuberculous Mycobacteria / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tuberculosis, Multidrug-Resistant / genetics
  • Tuberculosis, Multidrug-Resistant / metabolism*


  • ATP-Binding Cassette Transporters
  • Bacterial Proteins
  • Multidrug Resistance-Associated Proteins
  • Rv1258c protein, Mycobacterium tuberculosis
  • Adenosine Triphosphatases
  • phosphate import ATP-binding protein, Bacteria