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Emergence of Oxacillin Resistance in Stealth Methicillin-Resistant Staphylococcus aureus Due to mecA Sequence

Richard V Goering1, Erin A Swartzendruber2, Anne E Obradovich2

  • 1Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA richardgoering@creighton.edu.

Antimicrobial Agents and Chemotherapy
|May 22, 2019
PubMed

Insights

Oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) strains can develop resistance after antibiotic exposure due to secondary mecA mutations. This highlights the need for careful susceptibility testing to prevent treatment failures.

Area of Science:

  • Clinical Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA) strains present diagnostic challenges.
  • Mechanisms for oxacillin susceptibility in mecA-positive S. aureus are diverse.
  • OS-MRSA isolates are known to harbor the mecA gene but exhibit susceptibility to oxacillin and cefoxitin.

Purpose of the Study:

  • To identify nucleotide sequence changes responsible for the OS-MRSA phenotype.
  • To investigate the impact of subinhibitory antibiotic exposure on OS-MRSA.
  • To understand the genetic basis of oxacillin susceptibility in specific S. aureus isolates.

Main Methods:

  • Whole-genome sequencing of seven OS-MRSA clinical isolates from diverse geographical locations.
  • Analysis of six different spa types to understand genotypic diversity.
  • Characterization of mutations within the mecA gene and associated nucleotide repeat regions.

Main Results:

  • Oxacillin susceptibility in OS-MRSA was linked to mutations in nucleotide repeat regions within the mecA gene.
  • Subinhibitory antibiotic exposure induced secondary mutations in mecA, restoring oxacillin resistance.
  • Identified genetic variations contributing to the oxacillin-susceptible, yet mecA-positive, phenotype.

Conclusions:

  • OS-MRSA strains can transition to a resistant phenotype following antibiotic exposure.
  • Secondary mecA mutations are a key mechanism for resistance acquisition in these strains.
  • Follow-up susceptibility testing is crucial for OS-MRSA to detect potential resistance reversion and ensure effective treatment.
Keywords:
MRSAemergence of resistancemecAoxacillin susceptiblewhole-genome sequencing

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