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Second-site antibiotic resistance mutations in the ribosomal region of yeast mitochondrial DNA

J A Knight1, A J Courey, B Stebbins

  • 1Department of Biological Sciences, Mount Holyoke College, 01075, South Hadley, Massachusetts, USA.

Current Genetics
|November 5, 2013
PubMed

Insights

Mitochondrial erythromycin resistance can arise from mutations at a new locus, ery2, but requires a specific chloramphenicol resistance mutation (cap3) for expression. Other mutations map to the known ery1 locus.

Area of Science:

  • Mitochondrial genetics
  • Antibiotic resistance mechanisms
  • Molecular biology

Background:

  • Erythromycin resistance in mitochondria is primarily associated with the ery1 locus within the 21S rRNA gene.
  • Previous studies indicated that mutations at ery1 are the main cause of erythromycin resistance.
  • The role of other genetic loci and specific pre-existing mutations in conferring antibiotic resistance remains incompletely understood.

Purpose of the Study:

  • To investigate novel genetic loci responsible for spontaneous erythromycin resistance.
  • To determine the genetic basis of erythromycin resistance in yeast strains with pre-existing chloramphenicol resistance mutations.
  • To elucidate the interaction between chloramphenicol resistance mutations and the expression of erythromycin resistance.

Main Methods:

  • Isolation and characterization of spontaneous erythromycin-resistant mutants from a yeast strain with a cap3 chloramphenicol resistance mutation.
  • Genetic mapping of newly identified erythromycin resistance mutations to determine their allelic relationships and chromosomal locations.
  • Analysis of induced erythromycin-resistant mutants and comparison with spontaneous mutants.

Main Results:

  • A significant proportion of spontaneous erythromycin-resistant mutants did not map to the known ery1 locus.
  • These new mutations were allelic to each other and defined a novel locus, designated ery2.
  • Mutations at ery2 were found to be dependent on the cap3 chloramphenicol resistance mutation for the expression of erythromycin resistance.
  • Induced mutants and mutants from strains with a cap1 mutation predominantly mapped to ery1.

Conclusions:

  • The discovery of the ery2 locus expands our understanding of mitochondrial erythromycin resistance.
  • The cap3 mutation plays a crucial role in enabling erythromycin resistance mediated by mutations at the ery2 locus.
  • This suggests complex genetic interactions governing antibiotic resistance in mitochondria.

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