Capsular specificity

For a summary of earlier preparations of Type I capsular specific pol3fsaccharide, see B. White, The Biology of Pneumococcus, The Commonwealth Fund, Now York, N. Y.,M938,fp. 277. 

The cross-reactions of Types VII and XVIII Pneumococci and their respective antisera appeared to depend on the presence of multiple residues of (1—>4)-linked D-glucose. This contention was supported by the heavier precipitation of anti-Pn XVIII by reduced SVIII in which (1->1)-linked D-glucuronic acid had been converted to D-glucose. The cross-agglutination between Types VII and XVIII may also be due to the presence in both capsular specific pol3rsaccharides of similarly linked D-glucose residues. ... 

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. 

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. 

The type-specific capsular polysaccharide from Streptococcus pneumoniae type 5 contains 2-acetamido-2,6-dideoxy- -D-x>>/o-hexopyranosyl-4-ulose residues (17). Sugar nucleotides of hexos-4-uloses are important intermediates in the transformation of sugars during the biosynthesis, but this is the only known example of such a sugar as a polysaccharide component. 

There are solitary examples of other alditol phosphates as components of this class of polymers. Arabinitol 1-phosphate is part of the S. pneumoniae type 17F capsular polysaccharide. o-Glucitol 6-phosphate is a component of the group-specific polysaccharide from group B Streptococcus, which has a most unusual, ramified structure. In a polysaccharide from Nocardia... 

A structural study on lipid A and the O-specific polysaccharide of the lipopoly-saccharide from a clinical isolate of Bacteroides vulgatus from a patient with Crohn s disease was conducted by Hashimoto and coworkers [39]. They separated two potent virulence factors, capsular polysaccharide (CPS) and lipopolysaccharide (LPS), from a clinical isolate of B. vulgatus and characterized the structure of CPS. Next, they elucidated the strucmres of O-antigen polysaccharide (OPS) and lipid A in the LPS. LPS was subjected to weak acid hydrolysis to produce the lipid A fraction and polysaccharide fraction. Lipid A was isolated by PLC, and its structure was determined by MS and NMR. 

There are two pneumococcal vaccines, a 7-valent conjugated vaccine for children younger than 6 years of age and a 23-purified-capsular polysaccharide antigen vaccine for adults. The 23 capsular types in the vaccine represent at least 85% to 90% of the serotypes that cause invasive pneumococcal infections among children and adults in the United States.41 After vaccination, an antigen-specific antibody response, indicated by a twofold or greater rise in serotype-specific antibody, develops within 2 to 3 weeks in 80% or more of healthy young adults.42... 

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. 

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. 

The C-substance is a species-specific antigen of Streptococcus pneumoniae that often contaminates the type-specific capsular poly-... 

Clearly, further studies will be necessary to sort out the multiple factors involved in the in vivo immune response to C. neoformans carbohydrate-mimetic peptides. Several conclusions may be drawn from the results to date. Peptides that mimic the cryptococcal capsular polysaccharide show specificity, in that each peptide binds with differing affinity to closely related mAbs [140,149]. The pattern of binding to protective and nonprotective mAbs differs between the mimetic peptides and the polysaccharide [140]. Protective efficacy is related to the location of carbohydrate epitopes recognized by these mAbs, within the polysaccharide capsule, but hkely also depends on interactions between mAbs and cellular responses [149]. Peptides have been shown to be functional, immunogenic mimics, but their protective efficacy depends on multiple factors, including the type of Abs elicited and interactions with the cellular immune system. Protective efficacy does not correlate with binding affinity to representative mAbs, but rather depends on the nature of these interactions. 

It was no easy task, consuming years of careful, dedicated work. In a letter to his brother, Avery notes To try to find in that complex mixture, the active principle Try to isolate and identify the particular substance that will by itself when brought into contact with the R cell derived from Type II cause it to elaborate Type III capsular polysaccharide, and to acquire all the aristocratic distinctions of the same specific type of cells as that from which the extract was prepared Some job—full of headaches and heart breaks. But at last perhaps we have it. ... 

Viruses essentially consist of genetic material (nucleic acids, green strands in (A) and a capsular envelope made up of proteins (blue hexagons), often with a coat (gray ring) of a phospholipid (PL) bilayer with embedded proteins (small blue bars). They lack a metabolic system but depend on the infected cell for their growth and replication. Targeted therapeutic suppression of viral replication requires selective inhibition of those metabolic processes that specifically serve viral replication in infected cells. 

Epimerization at C-2 of UDP-GlcNAc, leading to the UDP derivative of 2-acetamido-2-deoxy-D-mannose, was also observed115 118 the monosaccharide was identified as a constituent of several capsular polysaccharides from Streptococcus pneumonia119-122 and Neisseria meningitidis group A (Ref. 123), the teichuronic acid of Bacillus cereus,124 and the O-specific... 

Deoxy-L-g/ycero-pentulosonic acid was found to be present in Klebsiella K38 polysaccharide249 and 3-deoxy-D-threo-hexulosonic acid was identified as a component of Azotobacter capsular polysaccharide.2S0 O-Specific polysaccharides of Pseudomonas aeruginosa and Shigella boydii were shown2SI... 

The disaccharide fragments listed in this Table are not found in the polysaccharides of Gram-positive cell-walls. For references on the structures of O-specific and capsular polysaccharides mentioned in this Table, see Refs. 98 and 276. b The total number of isomeric, disaccharide fragments identified in different polymers is shown in parentheses. 

Some results of studies on the biosynthesis of two other Klebsiella capsular polysaccharides have also been reported. In the case of type 2 specific polysaccharide336 (27), incorporation of the D-mannosyl group from GDP-Man into glycosyl-lipids and the polymer, catalyzed by a cell-envelope... 

The block mechanism of chain assembly is characteristic for polymeric chains of the UGT type (see Salmonella O-specific polysaccharides 10-12 and 18) and the UG type (see capsular polysaccharides 25, 27, and 33), with UDP-activated sugars serving as initiators of chain growth. It seems rather safe to suggest that the biosynthesis of other polymers of these types occurs through a block mechanism as well. 

Studies on the white clover -Rhizobium trifolii interaction are the most advanced. Trifoliin A, a lectin present in clover-seedling roots, binds hapten reversibly to carbohydrate antigens cross-reactive on the capsular polysaccharide of R. trifolii and clover epidermal-cells.244 A specific hapten that inhibits binding of trifoliin A to both surfaces is 2-deoxy-D-arabino-hexose.245 It has also been shown that levels of trifoliin A on root hairs decline with increasing concentrations of nitrate, in parallel to root-nodule development,246 and that lectin receptors are transient on R. trifolii, in a way coinciding with its capacity to be adsorbed to clover roots.247... 

All the KDO containing capsular polysaccharides shown in Figure 10 cross react in conventional antisera, mainly due to the fact that O-acetylation is never complete. In comparing native and modified polysaccharides we found that the immunodominant group in all these polysaccharides is KDO, acetylated or not. Closer serological study can be performed with monoclonal antibodies (Soderstrom, T, personal communication). It was found that a monoclonal K13 antibody reacts neither with the K20 nor with the K23 polysaccharides. Evidence was found that this antibody is specific for the P-(4-0-acetyl-KD0)-deter-minant of the K13 polysaccharide. 

Figure 18. Specific antibodies induced with derivatives of the capsular polysaccharide overcome bacteriaI self-defense by opsonization.

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