Accumulation of uridine and cytidine nucleotides in Staphylococcus aureus inhibited by gentian violet.

In 1949 Park and Johnson (1) reported the accumulation of labile phosphate esters in penicillin-inhibited Staphylococcus uureus. Later, the compounds which accumulate were identified as three uridine nucleotides (2). Compound 1 (UDP-GNAclactic)1 contains uridine 5’-pyrophosphate linked to an N-acetylamino sugar substituted in an ether linkage with lactic acid (GNAc-lactic). Compound 2 (UDP-GNAc-lactyl-ala) contains an amino acid (L-alanine) linked to UDP-GNAc-lactic through the carboxyl group in the lactic acid moiety, and Compound 3 (UDP-GNAc-lactyl-peptide) contains a peptide composed of three residues of nn-alanine, one of n-glutamic acid and one of r&sine, the sequence of which is Ala. Glu. Lys. Ala. Ala (5-7). Several features of the structure of these nucleotides are very unusual, and at the time of their discovery their function was obscure. Some biological parameters of the accumulation process were compatible with the hypothesis that nucleotide accumulation was closely related to a point of attack of penicillin within the bacterial cell (8). In the last few years, a great deal of information has accumulated relative to the composition of the bacterial cell wall, the structure bounded internally by the cytoplasmic membrane and externally, in some bacteria, by a capsule. Some of the same structural features were present in the walls of many grampositive bacteria as were found in the uridine nucleotides. A careful quantitative analysis of the walls of two strains of X. aureus which accumulate uridine nucleotides in the presence of penicillin was, therefore, carried out (9). From their composition it was evident that the walls contained the same N-acetylamino sugar-peptide fragment as was found in the uridine nucleotide. It seems likely, therefore, that the uridine nucleotide is a precursor of the bacterial cell wall in X. aureus, UDP serving to activate the N-acetylamino sugar fragment for incorporation into a cell wall precursor. Their accumulation, therefore, may be the consequence of interference by penicillin in one or more of the reactions leading to synthesis of the bacterial cell wall, and