@entity3405 -specific resistant mutants of XXXX .

@entity3256 @entity11215 @entity3405 @entity114 @entity794 @entity3524 @entity7265
In an approach to understanding the origin of @entity3256 resistance in clinical isolates of staphylococci, a series of @entity794 mutants resistant to various @entity3405 antibiotics were isolated in the laboratory by antibiotic selection. Mutants with low- and intermediate-level resistance showed considerable specificity for the particular antibiotic used in the selection process ( @entity3256 , @entity3524 , @entity7265 , and @entity11215 ), and resistance in such mutants also showed alterations in the antibiotic binding capacities of @entity114 -binding proteins (PBPs). In each case the isolation of mutants resistant to high concentrations of antibiotics required sequential passage in gradually increasing concentrations of the drug. The acquisition of increasing levels of @entity3256 resistance was paralleled by a gradual decrease in the binding capacities of PBPs 2, 3, and, possibly, 1. In a highly @entity3256 -resistant mutant (MIC, 150 micrograms/ml), PBPs 2 and 3 were no longer detectable by the @entity114 binding assay. Instead, a new PBP of poor binding capacity and anomalous molecular size (about 78 kilodaltons [kDa]) appeared in these cells. This corresponds to the molecular size of PBP 2a, the unique PBP that appears to be the biochemical correlate of resistance in clinical isolates of @entity3256 -resistant @entity794 . Also, similar to the case of resistant clinical isolates, high-level @entity3405 resistance was highly pH dependent in the laboratory mutants. We compared the patterns of radioactive peptides generated by partial proteolysis from the @entity114 -labeled PBP 2 of antibiotic-susceptible staphylococci and from the 78-kDa PBP 2a of a resistant clinical strain. Although the patterns were clearly different, seven of the eight characteristic peptides generated from PBP 2 of the susceptible strain were also detectable among the peptides released from PBP 2a. The results suggest that the 78-kDa PBP 2a of the resistant clinical strain evolved from PBP 2 of antibiotic-susceptible staphylococci and that in PBP 2a of the clinical isolate mutational changes have resulted in extensive alterations near the @entity3405 binding site.
