Differential growth of epidemic methicillin-resistant Staphylococcus aureus in vancomycin

I Alshami1, R C Matthews, J F Burnie

  • 1Department of Medical Microbiology, Clinical Sciences Building 1, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.

Insights

Certain epidemic methicillin-resistant Staphylococcus aureus (EMRSA) strains can grow in high vancomycin levels, developing altered resistance and cell wall characteristics. This adaptation suggests multiple underlying resistance mechanisms in these important bacterial pathogens.

Area of Science:

  • Microbiology
  • Bacterial genetics
  • Antimicrobial resistance

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant public health threat.
  • Vancomycin is a critical antibiotic for treating MRSA infections.
  • Emergence of vancomycin resistance in MRSA strains is a growing concern.

Purpose of the Study:

  • To investigate the capacity of epidemic MRSA (EMRSA) strains to develop resistance to vancomycin.
  • To characterize the phenotypic and genotypic changes associated with vancomycin adaptation in EMRSA.
  • To explore potential mechanisms underlying vancomycin tolerance in MRSA.

Main Methods:

  • Exposure of 17 EMRSA isolates to increasing concentrations of vancomycin.
  • Population analysis to identify vancomycin-resistant subpopulations.
  • Assessment of resistance to lysostaphin and teicoplanin.
  • Phage sensitivity testing.
  • Cell wall diameter measurements.
  • Pulsed-field gel electrophoresis (PFGE) for genetic typing.
  • Methicillin resistance level determination.

Main Results:

  • Six EMRSA strains (1, 2, 8, 11, 12, 15) adapted to vancomycin, designated 1A, 2A, 8A, 11A, 12A, and 15A.
  • Adapted strains produced clones resistant to 32 µg/mL vancomycin; EMRSA 12A and 15A grew at 128 µg/mL.
  • Adaptation correlated with increased resistance to lysostaphin and teicoplanin, altered phage sensitivity, and increased cell wall diameter.
  • PFGE revealed genetic changes in most adapted EMRSAs, except for 8A and 15A.
  • Changes in methicillin resistance levels were observed in adapted strains.

Conclusions:

  • Multiple EMRSA strains exhibit the ability to adapt to vancomycin.
  • Vancomycin adaptation is associated with significant alterations in bacterial physiology and genetics.
  • The study suggests that diverse mechanisms contribute to vancomycin tolerance and resistance in EMRSA.
  • Further research is needed to fully elucidate these complex resistance pathways.

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