Biochemical basis of mupirocin resistance in strains of Staphylococcus aureus

T H Farmer1, J Gilbart, S W Elson

  • 1SmithKline Beecham Pharmaceuticals, Betchworth, Surrey, UK.

Insights

Mupirocin resistance in Staphylococcus aureus is primarily caused by modifications to the target enzyme, isoleucyl-tRNA synthetase (IRS). This study found a strong correlation between enzyme inhibition and antibiotic resistance levels in various bacterial strains.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Mupirocin is a crucial antibiotic for treating Staphylococcus aureus infections.
  • Understanding antibiotic resistance mechanisms is vital for effective treatment strategies.

Purpose of the Study:

  • To investigate the mechanism of mupirocin resistance in Staphylococcus aureus.
  • To determine the correlation between mupirocin's effect on isoleucyl-tRNA synthetase (IRS) and bacterial resistance levels.

Main Methods:

  • Examined 21 Staphylococcus aureus strains with varying mupirocin resistance.
  • Assessed the time-dependent inhibition of isoleucyl-tRNA synthetase (IRS) by mupirocin.
  • Correlated minimum inhibitory concentrations (MICs) with IRS inhibition (I50) values.

Main Results:

  • Mupirocin demonstrated time-dependent inhibition of IRS, with greater inhibition in sensitive strains.
  • IRS I50 values strongly correlated with mupirocin MICs across sensitive, moderately resistant, and highly resistant strains.
  • No mupirocin degradation was observed in resistant S. aureus cell-free extracts.

Conclusions:

  • Modified isoleucyl-tRNA synthetase (IRS) enzyme is the primary mechanism conferring mupirocin resistance in the studied Staphylococcus aureus strains.
  • The study highlights the importance of IRS enzyme modification in bacterial antibiotic resistance.

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