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

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Diversity of penicillin-binding proteins. Resistance factor FmtA of Staphylococcus aureus

Xin Fan1, Yuhong Liu, Daryl Smith

  • 1Department of Chemistry, York University, Toronto, Ontario M3J 1P3, Canada.

The Journal of Biological Chemistry
|October 11, 2007
PubMed

Insights

FmtA, a protein in methicillin-resistant Staphylococcus aureus, interacts with beta-lactam antibiotics. This interaction suggests FmtA may be a penicillin-binding protein crucial for antibiotic resistance.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Drug Resistance

Background:

  • Antibiotic-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), poses a significant public health threat.
  • Penicillin-binding protein 2a (PBP2a) is a key factor in MRSA's resistance to beta-lactam antibiotics.
  • The roles of other proteins contributing to high-level MRSA resistance remain largely unknown.

Purpose of the Study:

  • To investigate the function of the FmtA protein in methicillin resistance in Staphylococcus aureus.
  • To elucidate the mechanism by which FmtA interacts with beta-lactam antibiotics.

Main Methods:

  • Biochemical assays to study the interaction between FmtA and beta-lactam antibiotics.
  • Analysis of the active-site serine residue and its role in complex formation.
  • Investigation of FmtA's binding affinity and acylation rate with beta-lactams.
  • Conformational change studies of FmtA in the presence of beta-lactams.
  • In vitro binding assays of FmtA to peptidoglycan.

Main Results:

  • FmtA forms covalently bound complexes with beta-lactam antibiotics.
  • A conserved serine residue in FmtA acts as the active-site nucleophile.
  • FmtA exhibits low binding affinity and slow acylation rates for beta-lactams, indicating intrinsic resistance.
  • Beta-lactam exposure induces conformational changes in FmtA.
  • FmtA demonstrates binding to peptidoglycan in vitro.

Conclusions:

  • FmtA is identified as a putative penicillin-binding protein.
  • FmtA's properties suggest it contributes to intrinsic beta-lactam resistance.
  • FmtA may play a role in compensating for peptidoglycan biosynthesis under cell wall stress induced by beta-lactams.

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