Complex relationship between acquisition of beta-lactam resistance and loss of virulence in Streptococcus pneumoniae.

In a previous study of a murine peritonitis model, no Streptococcus pneumoniae strains were found that were both clinically penicillin resistant and virulent. This study assessed the relationship between acquired resistance and virulence in single- and double-isogenic penicillin-resistant (Peni-R) mutants obtained by transformation of a virulent penicillin-susceptible recipient strain with pbp2b and pbpX polymerase chain reaction fragments from a Peni-R donor strain. Sequence analysis results of the pbp2b and pbpX alleles from these strains were in keeping with acquired penicillin resistance. The virulence of these strains was significantly reduced, which shows a relationship between beta-lactam resistance and loss of virulence. The phenotype of the 23.2x mutant remained stable after in vivo passage, which suggests that the pbpX gene is involved in growth, whereas virulent revertants of the 23.2b and 23.2b.2x mutants had no change in MIC. Compensatory mutations are implicated in the revival of virulence.