[Mode of action of D-amino acids on the biosynthesis of peptidoglycan (author's transl)]

Abstract

The mechanism of growth inhibition by D-amino acids was studied. D-Serine at concentrations from 0.02-0.2 M was sufficient to cause partial growth inhibition in seven species of bacteria representing the four most common types of peptidoglycan. The inhibited cells displayed morphological alterations. In the nucleotide-activated peptidoglycan precursors of these cells, D-alanine residues in position 4 and/or 5 of the peptide moiety were partially or even completely replaced by D-serine. The peptidoglycan also contained D-serine instead of D-alanine, but the percentual content of D-serine was significantly lower than that in the precursors. In addition, the modified peptidoglycan was less cross-linked than the normal one. Four other D-amino acids (D-threonine, D-valine, D-leucine, D-methionine) at concentrations of about 0.2 M caused similar effects as did D-serine when applied to Corynebacterium callunae and Bacillus subtilis. Thus the mode of action of D-amino acids on peptidoglycan synthesis can be generally described as follows: in their presence, at growth inhibiting concentrations modified nucleotide-activated peptidoglycan precursors are formed in which D-alanine residues are replaced by the D-amino acids. They are less efficiently incorporated into peptidoglycan. A high percentage of the modified muropeptides remains non-cross-linked, since they are poor substrates for the transpeptidation reaction. In the majority of the organisms, cross-linking was decreased when D-alanine in position 4 of the peptide subunit was replaced, in two organisms (Corynebacterium insidiosum and Staphylococcus aureus) replacement in position 5 was most effective, however. The low extent of cross-linkage is consistent with the morphological aberrations of inhibited cells. In previous studies with glycine, results were described that were in close analogy to those obtained with D-amino acids. However, glycine can replace not only D-alanine residues in position 4 and 5 but also L-alanine in position 1 of the peptide subunit.