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Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria
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Biosensor for Detection of Antibiotic Resistant Staphylococcus Bacteria

Published on: May 8, 2013

High level oxacillin and vancomycin resistance and altered cell wall composition in Staphylococcus aureus carrying

Anatoly Severin1, Keiko Tabei, Fred Tenover

  • 1The Rockefeller University, New York, New York 10021, USA.

The Journal of Biological Chemistry
|November 14, 2003
PubMed

Insights

Methicillin-resistant Staphylococcus aureus (MRSA) strains expressing vancomycin resistance (VRSA) were studied. VanA expression in S. aureus alters peptidoglycan synthesis, and mecA and vanA resistance mechanisms operate independently.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • First identification of methicillin-resistant Staphylococcus aureus (MRSA) with the enterococcal vanA gene complex and high-level vancomycin resistance (VRSA) in clinical settings.
  • Existing knowledge of MRSA's mecA-based resistance targeting cell wall biosynthesis.
  • Need to understand vanA expression in S. aureus and its interaction with mecA.

Purpose of the Study:

  • To investigate the expression of the vanA gene in the heterologous S. aureus background.
  • To determine how vanA interacts with the existing mecA-based resistance mechanism in S. aureus.
  • To elucidate the impact of combined vanA and mecA resistance on cell wall biosynthesis.

Main Methods:

  • Transfer of the vanA-containing staphylococcal plasmid from a clinical VRSA strain (HIP11714) to an MRSA strain (COL).
  • Characterization of the resulting transconjugant (COLVA) for antibiotic resistance profiles.
  • Analysis of peptidoglycan structure and cell wall precursor pools in COLVA.
  • Experimental inactivation of the mecA gene in COLVA to assess its effect on vancomycin resistance.

Main Results:

  • The transconjugant COLVA exhibited high and homogeneous resistance to both oxacillin and vancomycin.
  • Vancomycin exposure in COLVA led to abnormal peptidoglycan, with pentapeptides replaced by tetrapeptides and altered branching.
  • Key cell wall precursors shifted from UDP-MurNAc-pentapeptide to UDP-MurNAc-depsipeptide and UDP-MurNAc-tetrapeptide.
  • Transposon inactivation of mecA abolished beta-lactam resistance but did not affect vancomycin resistance.

Conclusions:

  • The vanA gene complex can be effectively expressed in S. aureus, conferring high-level vancomycin resistance.
  • Combined expression of vanA and mecA in S. aureus results in distinct alterations to cell wall peptidoglycan synthesis.
  • The mecA and vanA antibiotic resistance mechanisms in S. aureus appear to utilize separate enzymatic pathways for cell wall assembly.

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