DRASTIC CHANGES IN THE PEPTIDOGLYCAN COMPOSITION OF PENICILLIN-RESISTANT LABORATORY MUTANTS OF STREPTOCOCCUS-PNEUMONIAE

The penicillin MIC of 2 Streptococcus pneumoniae clinical isolates was increased 100-fold (from 0.02 to 2.0 mu g/ml) and 20-fold (from 0.5 t o 10.0 mu g/ml) through gradual exposure of the bacteria to increasing concentrations of penicillin in the laboratory. In both mutants the a ffinity of all four high molecular mass penicillin binding proteins (P BPs) for penicillin was drastically reduced accompanied by major chang es in the composition of peptidoglycan as resolved by HPLC. The ratio of crosslinked to monomeric peptides became virtually inverted in the resistant cell walls with monomers representing two-thirds of the muro peptide species. The proportion of the crosslinked tri-tetra dimer, a major component of the cell wall of the original isolates, decreased t o one-third or one-sixth of its normal representation, while the amoun ts of tripeptide monomers with an alanyl-serine substitution on the ly sine epsilon amino group increased by close to a factor of two. The gr owth rates of both mutants decreased by a factor of approximately two, as compared to the original bacteria.