title: Flavone markedly affects phenotypic expression of beta-lactam resistance in methicillin-resistant Staphylococcus aureus strains isolated clinically.
abstract: 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 beta-lactams. We named these compounds "ILSMR (intensifier of beta-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 beta-lactams, with COL serving as a reference. Neither SCCmec typing nor coagulase typing explained the diverse effects of flavone on the beta-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 beta-lactam resistance to MRSA strains, independently of an interaction with the mecA-encoded penicillin-binding protein 2a or with the beta-lactamase.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Shibata
authors.forename: Chikako
authors.initials: C
authors.lastname: Shirakata
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sato
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kuwahara
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Naokatu
authors.initials: N
authors.lastname: Arakaki
authors.forename: Tomihiko
authors.initials: T
authors.lastname: Higuti
mesh_terms: D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D016106:Methicillin Resistance / Q000187:drug effects* / Q000235:genetics; D008826:Microbial Sensitivity Tests / Q000379:methods; D010641:Phenotype; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018440:beta-Lactam Resistance / Q000187:drug effects / Q000235:genetics
chemical_list: D005419:Flavonoids