A. Severin et al., DRASTIC CHANGES IN THE PEPTIDOGLYCAN COMPOSITION OF PENICILLIN-RESISTANT LABORATORY MUTANTS OF STREPTOCOCCUS-PNEUMONIAE, FEMS microbiology letters, 130(1), 1995, pp. 31-35
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.