Suppression of beta-lactam antibiotic resistance in a methicillin-resistant Staphylococcus aureus through synergic action of early cell wall inhibitors and some other antibiotics

J Antimicrob Chemother. 1997 May;39 Suppl A:47-51. doi: 10.1093/jac/39.suppl_1.47.


We tested the effect of a number of mechanistically distinct antibacterial agents on the expression of methicillin resistance in a highly and homogeneously resistant strain of methicillin-resistant Staphylococcus aureus. The antibiotics, used at 0.25 x MIC, included inhibitors of early steps in peptidoglycan synthesis (fosfomycin, beta-chloro-D-alanine, D-cycloserine); bacitracin; teicoplanin and vancomycin; beta-lactam inhibitors chosen on the basis of their relatively selective affinities for penicillin-binding proteins 1, 2, 3 and 4 of S. aureus (imipenem, cefotaxime, cephradine and cefoxitin); compounds that inhibit various steps in protein synthesis (tetracycline, chloramphenicol, gentamicin, erythromycin and quinupristin/dalfopristin) and an inhibitor of DNA gyrase (temafloxacin). All inhibitors of early cell wall synthesis caused reduction of methicillin resistance and change from the homogeneous to the heterogeneous methicillin-resistant phenotype. Similar effects were obtained with only cephradine out of the four beta-lactams tested, and with erythromycin and quinupristin/dalfopristin as well. The other inhibitors of protein synthesis and DNA gyrase had no effect.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Colony Count, Microbial
  • Cycloserine / pharmacology
  • Drug Synergism
  • Fosfomycin / pharmacology
  • Methicillin Resistance
  • Microbial Sensitivity Tests
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / growth & development
  • beta-Alanine / analogs & derivatives
  • beta-Alanine / pharmacology
  • beta-Lactam Resistance


  • Anti-Bacterial Agents
  • beta-Alanine
  • Fosfomycin
  • 3-chloroalanine
  • Cycloserine