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.

Enantioselective Utilization of D-Amino Acids by Deep-Sea Microorganisms

“…The optimum D-Val concentration for growth was 5–6 mM. Adverse effects of high concentrations of DAAs have been reported previously in a variety of bacteria (Teeri and Josselyn, 1953 ; Bopp, 1965 ; Champney and Jensen, 1970 ; Cosloy and McFall, 1973 ; Yabu and Huempfner, 1974 ; White, 1979 ). The growth of strain A04V was also completely inhibited in the presence of >10 mM D-Val.…”

Synthesis of Chiral Gold Nanoparticle by Direct Reduction with L and D-Serine and Enhanced Anti-Mycobacterial Activity by D-Serine Protected Gold Nanoparticle

“…D-serine has long been reported to have an inhibitory activity against different species of Mycobacteria and some other bacteria from different genus. It is reported that D-serine inhibits the racemization of alanine by inhibiting alanine racemase, an enzyme essential for the synthesis of uridine diphosphate-N-acetylmuramylpentapeptide, a precursor of cell wall mucopeptide and thus inhibit cell wall synthesis in several bacteria [30]. The current study also reports an enhancement of anti-mycobacterial activity of D-serine when delivered as GNPcoated with this amino acid.…”

Inhibition of Growth and Cell Wall Synthesis of Mycobacterium smegmatis by D‐Threonine

“…These effects were similar to the effects of glycine' (1,5,6), which is an inhibitor of D-alanyl-D-alanine synthetase which is essential for synthesis of the cell wall mucopeptide precursor (2,8). Inhibition of the cell wall synthesis caused by D-threonine resembled that of D-serine in inhibiting the formation of diaminopimelic acid of the cell wall mucopeptide (9). The present investigation was designed to elucidate the effects of D-threonine on the morphology and cell wall mucopeptide synthesis.…”

“…Electron microscopic studies revealed that the surface of these cells was covered by cell wall. It thus seems that structural alteration of the cell wall caused by Dthreonine may be less profound and differs in some characteristics from that caused by glycine (1) or D-serine (9).…”

“…The culture conditions and methods Used for measurement of growth, intracellular accumulation of N-acylaminosugar, and incorporation of radioactive amino acids into cell wall mucopeptide were as described previously (9).…”