Suppression of beta-lactam antibiotic resistance in a methicillin-resistant Staphylococcus aureus through synergic action of early cell wall inhibitors and some other antibiotics.
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.
Sieradzki
K
K
Rockefeller University, New York, NY 10021, USA.
Tomasz
A
A
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D003523:Cycloserine / Q000494:pharmacology; D004357:Drug Synergism; D005578:Fosfomycin / Q000494:pharmacology; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D018440:beta-Lactam Resistance
D000900:Anti-Bacterial Agents; D015091:beta-Alanine; D005578:Fosfomycin; C006977:3-chloroalanine; D003523:Cycloserine