Composition of the Cell Wall of Staphylococcus aureus: Its Relation to the Mechanism of Action of Penicillin

Abstract

The bacterial cell wall is the rigid membrane which shapes and protects microorganisms. It is external to the cytoplasmic membrane, and internal to the capsule possessed by some microorganisms. Several procedures have been developed for preparing thii structure in a relatively pure form (1) , and qualitative analyses of its composition in various species have been carried out (2-5). The walls of gram-positive bacteria, which represent about 20 y0 of the dry weight of the cells, have a relatively simple composition as compared tc the more complex walls of gramnegative organisms (2, 3). Unusual features are the occurrence in bacterial cell walls of the unusual n-forms of several amino acids (6-S), of cu,e-diiminopimelic acid (9) and of a previously unknown lactic acid ether of acetylglucosamine which has been named acetylmuramic acid (10). Some strains of Staphylococcus aureus, when inhibited by penicillm, accumulate three uridine nucleotidea. The principal compound of this type contains an acetylamino sugar-peptide fragment linked tc uridine diphosphate through carbon atom 1 of the sugar (11). Biological features of the accumulation process are compatible with the hypothesis that nucleotide accumulation is closely related to a point of attack of penicillin within the bacterial cell (11, 12). The nucleotides which accumulate account for a considerable fraction of the total cellular phosphate (11) and in one strain amount to more than 10% of the dry weight of the microorganisms (13). These facts imply that the metabolic process in which these compounds participate may be a pathway of considerable activity in the organism. Like the cell wall, the principal uridine nucleotide which accumulates also contains a previously unknown amino sugar (which will be shown to be acetyhnuramic acid) and amino acids, some of which are in the unusual n-configuration. A careful study of the composition of the cell walls of two strains of S. aureus from which the uridine nucleotide had been isolated was, therefore, carried out and is reported here. The striking similarity of the composition of part of the wall and of the acetylmuramic acid-peptide fragment of the nucleotide suggested that the nucleotide may be a precursor of the bacterial cell wall. These findings have led to the hypothesis that the mechanism of action of penicillin is related tc inhibition of a step in biosynthesis of the bacterial cell wall (14).