Pneumococcus, capsular polysaccharide

By 1945, Stacey speculated about the possibility of a structural relationship between Pneumococcus capsular polysaccharides and those produced by other organisms. With Miss Schliichterer, he had examined the capsular polysaccharide of Rhizobium radicicolum. This polysaccharide gave a precipitin reaction in high dilution, not only with Type III Pneumococcus antiserum, but also mixed with antisera from other Pneumococcus types. The chemical evidence indicated that the polysaccharide resembled the specific polysaccharides of Types I and II Pneumococcus. A decade later, the acidic capsular polysaccharide from Azoto-bacter chroococcum, a soil organism, was studied. It, too, produced serological cross-reactions with certain pneumococcal specific antisera. Although the molecular structure of the polysaccharide was not established, adequate evidence was accumulated to show a structural relationship to Type III Pneumococcus-specific polysaccharide. This was sufficiently close to account for the Type III serological cross-relationship. 

Sulfonamide Drugs and Pneumococcus Capsular Polysaccharides, M. Stacey and E. Schliichterer, Nature. 143 (1939)724. 

Structure of Pneumococcus Capsular Polysaccharides, S. A. Barker and M. Stacey, Biochem. /., 82... 

Prevnar is a glycoconjugate heptavalent pneumococcal vaccine for young children made from the polysaccharide capsule of the pneumococcus (20). Although older vaccines made from pneumococcus capsular polysaccharide are available for adults, young children cannot make antibodies to the capsule. By coupling the pneumococcal capsular polysaccharide with a protein carrier, a vaccine was created that will trigger an infant s immune system to produce antibodies. 

Fucosamine. 2 Amino-216 dideoxygafactose. C6-H,jN04 mol wt 163,17. C 44.16%, H 8.03%, N 8 58%, O 39.22%. Isoln of D-form from lipopolysaccharide of CTiro-mobacterium vioiaceutn Crumpton, Davies. Biochem. J, 70, 729 (1958) from Bacillus lieheniformis Sharon et al, ibid. 93, 210 (1964), Isoln of L-foriti from type V Pneumococcus capsular polysaccharide Barker et al. Nature 189, 303... 

Constit. of type V Pneumococcus capsular polysaccharide and the mucopolysaccharide of Citrobacter freundii. 

In 1967, Heidelberger, Stacey et al. reported the purification, some structural features, and the chemical modification of the capsular polysaccharide from Pneumococcus Type I. Difficulties of direct hydrolysis of the polysaccharide were overcome and it was possible to identify some of the fragments in the hy-drolyzate. At least six products resulted from nitrous acid deamination. Two were disaccharides, which were identified, and sequences of linked sugar units were proposed. As modification of the polysaccharide decreased the amounts of antibody precipitated by anti-pneumococcal Type I sera, the importance of the unmodified structural features in contributing to the specificity of the polysaccharide was indicated. 

L-Fucosamine was found as a constituent of Pneumococcus Type V capsular polysaccharide and as a constituent of the mucopolysaccharides (glycosamino-glycans) of certain enteric bacteria A new synthesis was devised to make the amino sugar more available. 

Type IV Pneumococcus Specific Polysaccharide.—This capsular material110 ([ck]d + 33°, water) has been hydrolyzed and shown to contain units of D-glucose and N-acetyl-hexosamine. Its structure has not yet been studied. 

Reeves and Goebel72 have shown that hydrolysis of the reduced methylated capsular polysaccharide of Type III pneumococcus yields 2,3,6-trimethyl-D-glucose and the anomeric forms of methyl 2,4-dimethyl-D-glucoside. The cellobiuronic acid units in the polysaccharide are thus linked through position 3 of the D-glucuronic acid residue, probably by /3-D-linkages. That is, the polysaccharide contains alternate 1,3-and l,4-/3-D-linkages. 

The pneumococci all belong to different types of the same species, namely, Streptococcus pneumoniae. This was earlier called Diplococcus pneumoniae, but has been renamed.5 6 7 There are some 80 different types of pneumococcus, and two systems of nomenclature, the Danish, used in Europe, and Eddy s, used in the United States.8 Tables correlating the Danish and American designations have been published.8 The Danish system, with Arabic numerals and common abbreviations, such as Phi for Type 1 and SI for its type-specific, capsular polysaccharide, will be used in this article. 

Catalytic reduction and methanolysis of the methylated capsular polysaccharide of Type III pneumococcus gives a mixture of methyl 2,3,6-trimethyl- and 2,4-dimethyl-a/3-D-glucopyranosides. The latter, which arises from glucuronic acid units in the polysaccharide, can be separated into crystalline a- and 6-isomers identical with synthetic specimens.84,88... 

The separation and identification of disaccharides is often an important step in the elucidation of the structure of a natural polysaccharide, and Percival484 has published useful data on the O-trimethyl-silyl derivatives of a variety of disaccharides and their reduction products. In some instances, the trimethylsilyl ethers of the disaccharide alditols have lower retention times than those of the disaccharide derivatives. The per-O-trimethylsilyl derivatives of gentiobi-itol and maltitol were encountered in studies on the structure of Pneumococcus Type II capsular polysaccharide.4843... 

The work of Baddiley and collaborators256 259 on teichoic acids provides excellent examples of the use of deamination in the elucidation of oligosaccharide structure. For example, when treated with nitrous acid (see Scheme 9), the hexasaccharide 140, the repeating unit of the Pneumococcus Type XA capsular polysaccharide, gave 2-... 

Oxidation of the carboxyl-reduced and acetylated Pneumococcus type 2 capsular polysaccharide revealed that only one L-rhamnose residue in the hexasaccharide repeating-unit, later demonstrated to have the structure 60, was oxidized and, consequently, /3-L-linked.156 Replacement of 2,3,6-tri-O-methyl-D-glucose in the methylation analysis of the original polysaccharide by 2,3,4,6-tetra-O-methyl-D-glucose in that of the oxidized polysaccharide established that this L-rhamnose residue is linked to 0-4 of a D-glucose residue. The analysis also showed that it was an L-rhamnose residue in the chain (and not the branching L-rhamnose residue) that was /3-linked. 

A polymaltose prepared by Ricketts and Rowe140 reacted with pneumococcus Type XII antiserum more extensively than did a polyglucose prepared by the same authors, but both polysaccharides left behind some antibody reactive with glycogen. Neither polymer reacted with Type II antiserum. Polygalactose gave a slight precipitate with Type IV antiserum, the capsular polysaccharide of which is known to contain D-galactose. 

The uridine diphosphate ester derivatives in a non-capsulated. Type II pneumococcus and a capsulated. Type III pneumococcus were investigated by Smith, Mills, and Harper." The capsule of the Type III pneumococcus is composed of a polysaccharide having 4-0-( 8-D-glucopyranosyluronic acid)-D-glucose as a repeating unit. n-Glucuronic acid, D-glucose, and L-rhamnose are constituents of the capsular polysaccharide of the Type II pneumococcus. 

The 6-trityl ether of methyl 3-tosyl-D-glucopyranoside was employed by Goebel and coworkers for the unequivocal synthesis of methyl 2,4-dimethyl- 9-D-glucopyranoside. This synthesis was an important link in elucidating the structure of the capsular polysaccharide of Type III pneumococcus. 

Pneumococcus Group or C) Polysaccharide.—This substance, fajo -h 61° (water), is the polysaccharide constituent of the somatic part of the cell, and is common to all the pneumococcus types. It shows group specificity and is generally similar to the Type IV capsular polysaccharide. Its constituent units are probably N-acetyl-D-glucosamine, a hexose and phosphoric acid. It may be termed the carbohydrate residue of the heterophile antigen (described below) of pneumococcus which was separated by Goebel and his coworkers. 

Reeves and Goebel have shown that hydrolysis of the reduced methylated capsular polysaccharide of Type III pneumococcus yields... 

In view of certain structural similarities, it is appropriate to consider these polysaccharides together. The acidic, capsular polysaccharide of Type III pneumococcus ([a]n —32.2° acid equivalent, 346 and nitrogen, 0.05%) is precipitable by barium hydroxide, heavy-metal salts, and hydrochloric acid. On acidic hydrolysis, it yields a small proportion of D-glucose together with an aldobiouronic acid identified as cello-biouronic acid [4-0-(/3-D-glucopyranosyluronic acid)-D-glucopyranose] by methylation and hydrolysis. Optical rotation data suggested that the... 

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