A link in transcription between the native pbpB and the acquired mecA gene in a strain of Staphylococcus aureus

Susana Gardete1,2, Hermínia de Lencastre1,2, Alexander Tomasz1

  • 1Laboratory of Microbiology, The Rockefeller University, 1230 York Avenue, NY 10021, USA.

Insights

Interrupted penicillin-binding protein B (pbpB) transcription halts Staphylococcus aureus growth and causes lysis in MSSA strains, while MRSA strains show slower growth and reduced PBP2A levels.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Bacterial Genetics

Background:

  • Penicillin-binding proteins (PBPs) are crucial for bacterial cell wall synthesis.
  • Meticillin resistance in Staphylococcus aureus (MRSA) is mediated by the mecA gene, encoding PBP2A.
  • Understanding the regulation of pbpB and its interplay with mecA is vital for developing new antimicrobial strategies.

Purpose of the Study:

  • To investigate the differential effects of pbpB transcription interruption on methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus.
  • To elucidate the regulatory relationship between pbpB transcription and the expression of the mecA resistance gene.

Main Methods:

  • Utilized IPTG-inducible conditional mutants of pbpB in both MSSA and MRSA strains.
  • Monitored bacterial growth, cell lysis, and morphology.
  • Quantified penicillin-binding protein (PBP) 2 and PBP2A levels.
  • Assessed mecA transcript abundance using promoter fusion experiments and transcript analysis.

Main Results:

  • In MSSA, pbpB interruption led to rapid growth arrest, cell lysis, and decreased PBP2 quantities.
  • MRSA strains exhibited prolonged survival with increasing doubling times, reduced PBP2A, and declining mecA transcript levels.
  • Re-introduction of IPTG restored pbpB transcription, followed by increased mecA transcription, suggesting a regulatory link.

Conclusions:

  • pbpB transcription plays a critical role in the viability of MSSA, while MRSA exhibits a more complex response due to PBP2A.
  • The mecA resistance gene's transcription appears to be regulated by signals associated with pbpB transcription changes in Staphylococcus aureus.

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