eis Promoter C14G and C15G Mutations Do Not Confer Kanamycin Resistance in Mycobacterium tuberculosis

Suporn Pholwat1, Suzanne Stroup1, Scott Heysell1

  • 1Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.

Insights

Specific mutations in the eis gene significantly impact Mycobacterium tuberculosis resistance to kanamycin. Identifying these eis mutations is crucial for accurate genotypic susceptibility testing for kanamycin treatment.

Area of Science:

  • Microbiology
  • Genetics
  • Drug Resistance

Background:

  • Mycobacterium tuberculosis (M. tuberculosis) poses a significant global health challenge.
  • Antimicrobial resistance in M. tuberculosis complicates treatment regimens.
  • The eis gene's role in drug resistance requires further elucidation.

Purpose of the Study:

  • To investigate the impact of specific eis promoter mutations on Mycobacterium tuberculosis drug resistance.
  • To determine the minimum inhibitory concentrations (MICs) for kanamycin and amikacin in recombinant M. tuberculosis strains with eis mutations.

Main Methods:

  • Utilized a specialized transduction strategy to create recombinant M. tuberculosis strains.
  • Introduced specific eis promoter mutations (C14T, C12T, G10A, C14G, C15G).
  • Determined kanamycin and amikacin MICs for each recombinant strain.

Main Results:

  • eis promoter mutations C14T, C12T, and G10A conferred kanamycin resistance (MICs 40, 10, and 20 μg/ml).
  • eis mutations C14G and C15G resulted in kanamycin susceptibility (MIC 2.5 to 5 μg/ml).
  • All tested eis mutants remained susceptible to amikacin (MIC 0.5 to 4 μg/ml).

Conclusions:

  • Specific eis mutations are directly linked to kanamycin resistance in M. tuberculosis.
  • Genotypic susceptibility testing for kanamycin requires the identification of these precise eis mutations.
  • Understanding eis mutation profiles can guide targeted M. tuberculosis treatment strategies.