Inhibition of Growth of Mycobacterium smegmatis and of Cell Wall Synthesis by d -Serine

Abstract

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.