Penicillin-binding proteins in β-lactam-resistant laboratory mutants of Streptococcus pneumoniae

The increasing number of penicillin-resistant clinical strains of Strepfococcus pneumoniae has raised questions about the mechanism involved. We have isolated a large number of independent, spontaneous laboratory mutants with increasing resistance against either piperacillin or cefotaxime. Both classes of mutants showed a different pathway of penicillin-binding protein (PBP) alterations, and within each group of mutants the individual PBPs appeared to have changed at different resistance levels and in different sequences. The mutations led to decreased β-lactam affinity and possibly to a reduction in the amount of protein present in the cell, but differences in apparent molecular weight, like those reported in low- and high-level resistant pathogenic strains, were not found. Some mutants showed a high degree of cross-resistance to a variety of pencillins and cephaiosporins independently of the acquired PBP alterations, indicating that different genotypes can be responsible for the same phenotypic expression of resistance.