SUPPRESSION OF GLYCOPEPTIDE RESISTANCE IN A HIGHLY TEICOPLANIN-RESISTANT MUTANT OF STAPHYLOCOCCUS-AUREUS BY TRANSPOSON INACTIVATION OF GENES INVOLVED IN CELL-WALL SYNTHESIS

The teicoplanin-resistant laboratory mutant TNM of Staphylococcus aure us strain COL (minimal inhibitory concentration for teicoplanin increa sed from 3 to 200 mu g/ml) produced an abnormal peptidoglycan in which the proportion of cross-linked oligomeric muropeptides (pentameric an d higher than pentameric species), representing similar to 60% of all muropeptide species in the parental strain, was reduced to similar to 17% in the mutant. In parallel, there was an increase in the represent ation of the monomeric muropeptides from 4% tin the parent) to 20% in the resistant strain. The mutant cell wall showed greatly increased po rosity for the detergent extraction of cytoplasmic proteins, and this property was abolished in a Tn551 insertional derivative of TNM, which was selected for reduced (parental level) teicoplanin resistance. Tra nsposon inactivation of the global regulatory genes Sigma-B and sar, a nd several genes involved in early steps of staphylococcal peptidoglyc an synthesis, all caused extensive reduction of teicoplanin resistance in mutant TNM, in some cases to levels close to or below the MIC valu e of the parental strain.