An elevated mutation frequency favors development of vancomycin resistance in Staphylococcus aureus

Area of Science:

• Microbiology
• Genetics
• Antimicrobial Resistance

Background:

• Intermediate vancomycin resistance in Staphylococcus aureus (S. aureus), particularly methicillin-resistant strains, is a significant clinical concern.
• Previous studies suggest stepwise mutations contribute to vancomycin resistance.
• Mutator strains with defective DNA mismatch repair may acquire adaptive mutations more rapidly.

Purpose of the Study:

• To investigate the role of an elevated mutation frequency in the rapid acquisition of vancomycin resistance in S. aureus.
• To compare the evolution of vancomycin resistance in a wild-type S. aureus strain versus its isogenic mutator mutant.

Main Methods:

• Stepwise vancomycin selection was applied to S. aureus RN4220 and its mutS-knockout mutator strain (RN4220ΔmutS).
• Resistance levels were determined by minimum inhibitory concentration (MIC).
• Changes in phage typeability, growth behavior, and regrowth at high vancomycin concentrations were assessed.

Main Results:

• Vancomycin resistance evolved significantly faster in the mutator strain (5 passages) compared to the wild type (19 passages).
• The mutator strain achieved a higher level of vancomycin resistance (MIC of 32 µg/ml) than the wild type (4 µg/ml).
• Susceptibility to other antibiotics, except teicoplanin, remained unchanged; however, increased resistance correlated with loss of phage typeability and altered growth.

Conclusions:

• An elevated mutation rate accelerates the development of vancomycin resistance in S. aureus.
• High mutation frequency is a contributing factor to the emergence of vancomycin resistance in S. aureus.
• This finding has implications for understanding and combating antimicrobial resistance.