Gentamicin-resistance determinants confer background-dependent hygromycin B resistance

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Characterizing Multidrug Efflux Systems in Acinetobacter baumannii Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System
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M Kojic1, N Milojevic, B Vasiljevic

  • 1Institute of Molecular Genetics and Genetic Engineering, Belgrade, Yugoslavia.

Microbial Drug Resistance (Larchmont, N.Y.)
|November 24, 1999
PubMed

Insights

Aminoglycoside-producing Micromonospora exhibit unexpected resistance to hygromycin B. This resistance is dependent on the specific strain and resistance genes, suggesting a novel mechanism beyond typical aminoglycoside resistance pathways.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antibiotic Resistance

Background:

  • Micromonospora strains producing aminoglycosides display resistance to similar antibiotics.
  • They are typically susceptible to aminoglycosides with different aminocyclitol substitutions.
  • Unexpectedly, these strains also showed resistance to hygromycin B, which has a distinct structure and mechanism of action.

Purpose of the Study:

  • To investigate the mechanism behind hygromycin B resistance in aminoglycoside-producing Micromonospora.
  • To determine if known aminoglycoside resistance genes confer hygromycin B resistance.
  • To explore the strain-dependent nature of this resistance.

Main Methods:

  • Cloning of resistance genes (sgm, grm) into heterologous hosts (Streptomyces lividans, E. coli).
  • Introduction of resistance genes into M. melanosporea.
  • Testing of transformants for resistance to various aminoglycosides, including hygromycin B.
  • Comparison of resistance gene expression across different bacterial backgrounds.

Main Results:

  • Cloned genes conferred expected aminoglycoside resistance in S. lividans and E. coli, but not hygromycin B resistance.
  • In M. melanosporea, the same genes conferred resistance to hygromycin B.
  • Only the kgm gene facilitated hygromycin B resistance, and only in the M. melanosporea background.
  • This highlights a strain-dependent expression of hygromycin B resistance.

Conclusions:

  • Aminoglycoside resistance in Micromonospora is not solely determined by the resistance genes but also by the host genetic background.
  • A novel mechanism for hygromycin B resistance exists in M. melanosporea, influenced by strain-specific factors.
  • Further research is needed to elucidate the precise mechanism of this background-dependent resistance.

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