Impairing methylations at ribosome RNA, a point mutation-dependent strategy for aminoglycoside resistance: the rsmG

Alfonso Benítez-Páez1, Sonia Cárdenas-Brito1, Mauricio Corredor2

  • 1Grupo de Análisis Bioinformático, GABi, Centro de Investigación y Desarrollo en Biotecnología, CIDBIO, Bogotá, D.C, Colombia.

Abstract

Insights

Mutations in the rsmG gene can lead to streptomycin resistance in bacteria. Further mutations in rpsL synergize with rsmG mutations to significantly increase streptomycin resistance, revealing a common resistance mechanism.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Aminoglycosides, such as streptomycin, inhibit bacterial translation by binding to ribosomal RNA.
  • Pathogens develop streptomycin resistance through mutations in non-structural ribosome genes, including RNA methylases like rsmG.
  • The rsmG gene encodes a methyltransferase essential for m7G527 modification in the 16S rRNA 530 loop, a streptomycin binding site crucial for ribosomal accuracy.

Purpose of the Study:

  • To investigate novel mutation hotspots that impair RsmG function and confer streptomycin resistance.
  • To understand the molecular and genetic mechanisms underlying aminoglycoside resistance, particularly high-level streptomycin resistance in rsmG mutants.

Main Methods:

  • Mutagenesis of the Escherichia coli rsmG gene.
  • Genotyping analysis of the rpsL gene in bacterial isolates exhibiting increased streptomycin resistance compared to parental strains.

Main Results:

  • Mutations in rpsL were frequently observed in streptomycin-resistant mutants.
  • A synergistic effect between rsmG and rpsL mutations was identified, significantly enhancing streptomycin resistance.

Conclusions:

  • This study elucidates a common mechanism of streptomycin resistance involving rsmG and rpsL.
  • The findings suggest this mechanism is potentially transferable to other ribosome RNA methylase genes involved in essential ribosomal modifications.

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