The Synthesis of Type III Pneumococcal Capsular Polysaccharide from Uridine Nucleotides by a Cell-free Extract of DipZococcus

In 1953, Bernheimer (1) showed that suspensions of resting Type III pneumococci could synthesize capsular polysaccharide from glucose or from certain other monosaccharides in a medium containing magnesium, potassium, and phosphate ions. Although a considerable amount of polysaccharide was synthesized from glucose, little or none was formed when glucose was replaced by sodium glucuronate or by sodium cellobiuronate. More recently it has been shown that the glucuronic acid and acetylglucosamine residues of the hyaluronic acid synthesized by Group A ,&hemolytic streptococci are derived from glucose without cleavage of the glucose molecule (2) and that uridine diphosphoglucuronic acid and uridine diphospho-N-acetylglucosamine are the immediate precursors of hyaluronic acid (3). These observations and those concerning the role of uridine pyrophosphoglycosyl compounds in the synthesis of chitin (4), cehulose (5), glycogen (6), and @-I ,3-glucan (7) make it probable that the donation of glycosyl groups from uridine pyrophosphoglycosyl compounds represents a general mechanism for the biosynthesis of polysaccharides. Previous investigations of the pneumococcus have revealed the presence of a number of uridine pyrophosphoglycosyl compounds in various types of this organism (8-10) and have shown that these uridine compounds are probably concerned in the synthesis of their polysaccharides. It has been found that, when the capsular polysaccharide of a particular type of pneumococcus contains uranic acid, the uridine pyrophospho-compound of that uranic acid is formed by cells of the pneumococcal type in-question. More recent genetic and biochemical studies have shown that the synthesis of certain types of pneumococcal capsular polysaccharide is dependent upon an intact pathway for the formation of uridine pyrophosphouronic acid (11) and that the lack of only one enzyme in such a pathway results in failure of the cell to form capsular polysaccharide in normal quantity. Type III pneumococcal capsular polysaccharidc is a polymer of cellobiuronic acid (/3-1,4-glucuronosido-glucose) and it appeared likely that uridine diphosphoglucose and uridine diphos-