Related Experiment Video
Updated: Aug 17, 2026

Subcutaneous Infection of Methicillin Resistant Staphylococcus Aureus (MRSA)
Published on: February 9, 2011
Biochemical basis of mupirocin resistance in strains of Staphylococcus aureus
T H Farmer1, J Gilbart, S W Elson
1SmithKline Beecham Pharmaceuticals, Betchworth, Surrey, UK.
Abstract:
Twenty one strains of Staphylococcus aureus, of varying resistance to mupirocin, were examined in order to determine the mechanism of resistance to this antibiotic; six of these strains were mupirocin sensitive (MIC 0.12-1.0 mg/L) nine moderately resistant strains (MIC 8-256 mg/L) and six highly resistant strains (MIC > 2048 mg/L). Mupirocin showed a time-dependent inhibition of the target enzyme, isoleucyl-tRNA synthetase (IRS); incubation of the antibiotic with this enzyme before adding the substrates markedly increased inhibition in sensitive strains. The IRS I50 values (the antibiotic concentrations which cause a 50% decrease in enzyme activity) correlated well with the MIC values for each strain (P < 0.01). The mean I50 value for sensitive strains was 3.3 x 10(-2) mg/L, in moderately resistant strains it was 1.3 x 10(-1) mg/L and in highly resistant strains it was 7.5 mg/L. No degradation of mupirocin could be detected during extended incubation of the antibiotic with cell free extracts from four resistant S. aureus strains. We conclude that the production of a modified IRS enzyme is the major cause of mupirocin resistance in the strains studied.
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.
Related Concept Videos
Mismatch Repair
Development of Antibiotic Resistance
Staphylococcal Skin Infections
Mechanism of Antibiotic Resistance in MRSA
Inhibitors of Bacterial Protein Synthesis
Clinical Significance of Antibiotic Resistance

