Flavone Markedly Affects Phenotypic Expression of β-Lactam Resistance in Methicillin-Resistant Staphylococcus aureus Strains Isolated Clinically

Flavone and its derivatives had very weak antibacterial effects on methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus, but dramatically intensified MRSA's susceptibility to β-lactams. We named these compounds ILSMR (intensifier of β-lactam-susceptibility in MRSA). We also found discrepancies among MRSA strains in their responses to flavone; some strains showed phenotypic susceptibility to methicillin while others showed phenotypic resistance to it. To understand the mechanism underlying this discrepancy, we characterized 20 MRSA strains in detail, analyzed their conventional and molecular typings, and examined each strain's resistance to β-lactams, with COL serving as a reference. Neither SCCmec typing nor coagulase typing explained the diverse effects of flavone on the β-lactam MICs of these strains. Likewise, changes in pulsed-field gel electrophoresis (PFGE) type were not associated with the profiles of ILSMR effects. However, the present observations suggest that the ILSMR effects on MRSA is strain-specific, and that this effect depends on an as-yet unknown mechanism that is essential for the expression of the phenotype conferring β-lactam resistance to MRSA strains, independently of an interaction with the mecA-encoded penicillin-binding protein 2a or with the β-lactamase.