5-Fluorouracil and mucopeptide biosynthesis by Staphylococcus aureus

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Abstract
5-Fluorouracil partially inhibits cell-wall mucopeptide synthesis by S. aureus strain 524. This inhibition can be prevented by the simultaneous presence of uracil or uridine. During incubation in the presence of 5-fluorouracil, compounds accumulate which contain bound amino sugar and are soluble in trichloroacetic acid; this accumulation is prevented by the simultaneous presence of uracil or uridine. The compounds containing bound amino sugars which have accumulated are not readily utilizable by the cell for mucopeptide synthesis when fluorouracil is removed. Fractionation of the material, soluble in trichloroacetic acid and containing bound amino sugars, revealed the presence of 4 compounds: (1) containing fluorouracil, P, muramic acid, alanine, glutamic acid and lysine with the molecular proportions of 1:2:1:3:1:1; (2) a fluorouridine-P-N-acetylglucosamine compound with molecular proportions of 1:2:1; (3) a mixture of fluorouridine-muramic acid-alanine compounds which has not been fractionated completely but is likely to be fluorouridine diphospho-N-acetylmuramic acid and (4) this compound linked to alanine. The concentration of fluorouracil seems to decide whether or not non-fluorinated uridine compounds of similar composition also accumulate. At higher concentrations of fluorouracil these were not found. The relationship of the accumulation of the fluorouridine compounds to the penicillin-induced formation of the corresponding non-fluorinated compounds is discussed.