Inhibition of growth of Mycobacterium smegmatis and of cell wall synthesis by D-serine.
d-Serine inhibited the growth of Mycobacterium smegmatis and induced the morphological alteration of the bacilli. The growth inhibitory action of d-serine was partially reduced by an equimolecular concentration of d-alanine. The combination of glycine with d-alanine reversed the growth inhibition produced by d-serine more than did d-alanine alone. In cells cultured in the presence of d-serine, the amounts of alanine, diaminopimelic acid, and glycine inserted into the cell wall mucopeptide were reduced, and serine was increased. The intracellular accumulation of a precursor of cell wall mucopeptide was increased by d-serine, and this accumulation was reduced by d-alanine. d-Serine competed with glycine for incorporation into the cell wall mucopeptide. The incorporation of l-aspartic acid into diaminopimelic acid residues in the cell wall mucopeptide was markedly inhibited by d-serine. Three mutants resistant to d-serine were isolated by nitrosoguanidine treatment. In these mutants the effects of d-serine on the sites of cell wall mucopeptide synthesis were all reduced. Thus, d-serine inhibition of the growth is due to replacement of glycine residues of the cell wall mucopeptide with d-serine and inhibition of the cell wall synthesis by blocking the formation of d-alanine and diaminopimelic acid.
Yabu
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D000596:Amino Acids / Q000032:analysis / Q000494:pharmacology; D000606:Amino Sugars / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects* / Q000378:metabolism; D003960:Diaminopimelic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D020102:Mycobacterium smegmatis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D012694:Serine / Q000494:pharmacology*
D000596:Amino Acids; D000606:Amino Sugars; D001224:Aspartic Acid; D012694:Serine; D003960:Diaminopimelic Acid; D005998:Glycine