Lipopolysaccharide Antigens of <i>Pseudomonas aeruginosa</i>

Horton, Derek; Riley, David; Samreth, Soth; Schweitzer, M. G.

doi:10.1021/bk-1983-0231.ch002

Cited by 5 publications

(5 citation statements)

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“…The 13C nuclear magnetic resonance spectrum of this polysaccharide presented in [30] was virtually identical to the spectrum obtained by us: thus, on the basis of structural analysis described in this paper it has to be admitted that the structure of the Fisher immunotype 1 polysaccharide suggested earlier was erroneous. This error was probably due to the high resistance of glycosidic linkages of galactosaminouronic acid derivatives towards hydrolysis, thus preventing their direct detection, and also to the presence of glucose in the core of P .…”

Section: Discussionsupporting

confidence: 74%

“…In conclusion, it should be noted that for the repeating unit of the P. aeruginosa immunotype 1 (Fisher) 0-specific polysaccharide there was recently proposed a structure of a linear trisaccharide built up of rhamnose, glucose and N-acetylquinovosamine residues and containing 0-acetyl and 0-formyl groups [30]. The 13C nuclear magnetic resonance spectrum of this polysaccharide presented in [30] was virtually identical to the spectrum obtained by us: thus, on the basis of structural analysis described in this paper it has to be admitted that the structure of the Fisher immunotype 1 polysaccharide suggested earlier was erroneous.…”

Section: Discussionmentioning

confidence: 99%

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Somatic antigens of Pseudomonas aeruginosa. The structure of the O-specific polysaccharide chains of lipopolysaccharides of P. aeruginosa serogroup O4 (Lanyi) and related serotype O6 (Habs) and immunotype 1 (Fisher)

et al. 1985

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Somatic antigens of Pseudomonas aeruginosa. The structure of the O-specific polysaccharide chains of lipopolysaccharides of P. aeruginosa serogroup O4 (Lanyi) and related serotype O6 (Habs) and immunotype 1 (Fisher)

et al. 1985

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“…Currently there are no licensed vaccines available against Pseudomonas aeruginosa , although there are many studies in this direction which have evaluated a range of antigens including outer-membrane proteins, O -polysaccharides, exopolysaccharides, toxins, pili, and flagella. , The chemical synthesis of a few glycans such as β- d -mannose containing oligosaccharide fragments related to its exopolysaccharide, pseudaminic acid containing the trisaccharide of Pseudomonas aeruginosa 1244 pilin glycan, and the d -rhamnose-containing trisaccharide related to the A band polysaccharide have been reported so far. The rare-sugar-containing trisaccharide repeating unit of P. aeruginosa O11 lipopolysaccharide with a proposed structure of →2)-β- d -Glc-(1 → 3)-α- l -FucNAc-(1 → 3)-β- d -FucNAc-(1→ (Figure ) is a potential vaccine candidate. , The chemical synthesis of conjugation-ready trisaccharide repeating unit 1 has not been reported yet and is highly warranted.…”

Section: Introductionmentioning

confidence: 99%

“…The raresugar-containing trisaccharide repeating unit of P. aeruginosa O11 lipopolysaccharide with a proposed structure of →2)-β-D- 1) is a potential vaccine candidate. 19,20 The chemical synthesis of conjugation-ready trisaccharide repeating unit 1 has not been reported yet and is highly warranted.…”

Section: Introductionmentioning

confidence: 99%

Total Syntheses of Conjugation-Ready Trisaccharide Repeating Units of Pseudomonas aeruginosa O11 and Staphylococcus aureus Type 5 Capsular Polysaccharide for Vaccine Development

2019

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Pseudomonas aeruginosa belongs to the group of three "critical priority" multi-drug-resistant pathogens listed by WHO and is responsible for severe and often deadly infections such as bloodstream infections and pneumonia. Staphylococcus aureus is also a "high priority" pathogen which is a major cause of serious nosocomial infections such as bacteremia, sepsis, and endocarditis. Owing to their ability to adapt resistance to almost any antibiotics, vaccines against these pathogens are urgently required. These pathogens express structurally unique and densely functionalized glycans on their surfaces which are absent on the host cells. Such carbohydrate antigens are valuable targets for the development of glycoconjugate vaccines and diagnostics. Here, we report the first total synthesis of the conjugation-ready trisaccharide repeating unit of Pseudomonas aeruginosa O11 via a highly stereoselective and efficient assembly of a rare Lfucosamine-and D-fucosamine-containing 1,2-cis-linked disaccharide motif and its regioselective glycosylation at O3. A systematic study was conducted for the notoriously difficult glycosylation with the most unreactive axial 4-OH of the rare disaccharide, and the successful outcome was utilized to accomplish the total synthesis of an aminopropyl linker-attached trisaccharide repeating unit of Staphylococcus aureus capsular polysaccharide type 5, which is also a potential antigen for immunotherapy and vaccine development. The judicious selection of protecting groups and reaction conditions allowed the stereoselective assembly and selective functional group interconversions to access the structurally complex linker-attached trisaccharide repeating units, which are valuable tools for immunological evaluation and vaccine development. The strategy is useful for the synthesis of other structurally related complex glycans.

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“…It now appears clear that serogroup definitions of O-antigenic activity do not correlate with the range of antigens needed for an effective vaccine based on immunogenic, nontoxic, high-molecular-weight versions of the O polysaccharides (13,33). The Fisher immunotyping schema was based on definitions of protective antigens obtained by immunization of mice with over 200 strains of P. aeruginosa and subsequent challenge with live organisms, but these studies used an extract later shown to be composed mostly of LPS (15). Detoxification of LPS by acid hydrolysis to eliminate the lipid A portion and isolation of the immunogenic high-molecular-weight polysaccharide O antigens, originally described in 1978 (33,35), have consistently resulted in monovalent preparations of O antigens that are immunogenic in mice (30,31,34,35) and humans (26,28).…”

Section: Discussionmentioning

confidence: 99%

Complex Serology and Immune Response of Mice to Variant High-Molecular-Weight O Polysaccharides Isolated from Pseudomonas aeruginosa Serogroup O2 Strains

Hatano

Pier

1998

Infect Immun

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The O antigen of the Pseudomonas aeruginosalipopolysaccharide is the optimal target for protective antibodies, but the unusual and complex nature of their sugar substituents has made it difficult to define the range of these structures needed in an effective vaccine. Most clinical isolates of P. aeruginosacan be classified into 10 O-antigen serogroups, but slight chemical differences among O polysaccharides within a serogroup give rise to subtype epitopes. These epitopes could impact the reactivity of O-antigen-specific antibodies, as well as the susceptibility of a target strain to protective, opsonic antibodies. To define parameters of serogroup and subtype-epitope immunogenicity, antigenicity, and surface expression on P. aeruginosa cells, we prepared high-molecular-weight O-polysaccharide vaccines from strains ofP. aeruginosa serogroup O2, for which eight structurally variant O antigens expressing six defined subtype epitopes (O2a to O2f) have been identified. A complex pattern of immune responses to these antigens was observed following vaccination of mice. The high-molecular-weight O polysaccharides were generally more immunogenic at low doses (1 and 10 μg) than at a high dose (50 μg) and usually elicited antibodies that opsonized the homologous strain for phagocytic killing. Some of the individual polysaccharides elicited cross-opsonic antibodies to a variable number of strains that express all of the defined serogroup O2 subtype epitopes. Combination into one vaccine of two antigens that individually elicited cross-reactive opsonic antibodies to most members of the O2 serogroup inhibited, instead of enhanced, the production of antibodies broadly reactive with most serogroup O2 subtype strains. Thus, immune responses to P. aeruginosa O antigens may be restricted to a limited range of epitopes on structurally complex O antigens, and combining multiple related antigens into a single vaccine formulation may inhibit the production of those antibodies best able to protect against mostP. aeruginosa strains within a given O-antigen serogroup.

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Lipopolysaccharide Antigens of Pseudomonas aeruginosa

Cited by 5 publications

References 0 publications

Somatic antigens of Pseudomonas aeruginosa. The structure of the O-specific polysaccharide chains of lipopolysaccharides of P. aeruginosa serogroup O4 (Lanyi) and related serotype O6 (Habs) and immunotype 1 (Fisher)

Somatic antigens of Pseudomonas aeruginosa. The structure of the O-specific polysaccharide chains of lipopolysaccharides of P. aeruginosa serogroup O4 (Lanyi) and related serotype O6 (Habs) and immunotype 1 (Fisher)

Total Syntheses of Conjugation-Ready Trisaccharide Repeating Units of Pseudomonas aeruginosa O11 and Staphylococcus aureus Type 5 Capsular Polysaccharide for Vaccine Development

Complex Serology and Immune Response of Mice to Variant High-Molecular-Weight O Polysaccharides Isolated from Pseudomonas aeruginosa Serogroup O2 Strains

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