Table 2.
Bacterial exopolysaccharides as virulence factors and drug and vaccine targets
| Exopolysaccharidea | Structure | Pathogen | Pathogenic mechanism | Potential drugs and targets | Vaccines on the market or in developmentb |
|---|---|---|---|---|---|
| Alginate | β-(1,4)-linked non-repeating heteropolymer of partially acetylated mannuronic acid and guluronic acid | Pseudomonas spp., Pseudomonas aeruginosa | Biofilm matrix component; antiphagocytic factor, protection from free radicals and antibiotics | Alginate oligomers induce a greater negative charge on the cell surface, reduce bacterial adherence and biofilm formation, bind to bacterial flagella and inhibit motility, and disrupt the extracellular polymeric matrix114,160c; alginate lyase degrades alginate and reduces the viscoelasticity of mucoid biofilms161; a class of mercaptobenzotriazoloquinazolinones inhibits the Alg44–c-di-GMP interaction and alginate production112 | Polymannuronic acid; alginate; conjugated with various carriers; AR-105c,d (IgG1 mAb) targets alginate |
| Pel | Partially acetylated (1→4)-glycosidic linkages of N-acetylgalactosamine and N-acetylglucosamine | P. aeruginosa | Biofilm matrix component; protection from certain aminoglycoside antibiotics | The glycoside hydrolase PelAh targets Pel and inhibits biofilm formation, reduces biofilm thickness and increases neutrophil killing162 | NA |
| Psl | Repeating pentasaccharide of d-mannose, d-glucose and l-rhamnose | P. aeruginosa | Adhesion of cells to surface for biofilm formation; protection from phagocytosis, oxidative stress and antibiotics | The glycoside hydrolase PslGh inhibits biofilm formation and reduces biofilm thickness162 | MEDI3902d (IgG1 mAb) targets Psl |
| Cellulose | β-(1,4)-linked homopolymer of d-glucose | Many enterobacterial species (for example, Escherichia coli, Salmonella enterica and Citrobacter freundii) | Biofilm matrix component; phosphoethanolamine cellulose has a mortar-like function and stabilizes curli attachment to bladder cells; protects Salmonella enterica subsp. enterica serovar Typhimurium inside macrophages; antiphagocytic factor | NA | NA |
| Hyaluronate | β-(1,4)-linked repeating heteropolymer of glucoronate and N-acetylglucosamine | Group A and group C Streptococcus spp.; Bacillus cereus G9241; Pasteurella multocida Carter type A | Biofilm matrix component; antiphagocytic factor; supports pneumococcal growth on digestion | NA | Group A Streptococcus: Lancefield group A carbohydrate conjugated with TT carrier; N-acetylglucosamine -deficient polysaccharide conjugated with recombinant pneumococcal protein SP0435 |
| K antigens (CPS) | >80 serotypes; differ from each other by their sugar composition, linkage between the sugars and their stereoisomeric formse | E. coli (groups 1, 2, 3 and 4) | Capsular; antiphagocytic factor; some are structurally similar to host cell polysaccharides; adhesion to the host cells; anionic CPS binds cationic antimicrobial peptides and prevents cell lysis | Unnatural cyclic octasaccharide (6-deoxy-6-amino) cyclomaltooctaose inhibits K30 polysaccharide transport in E. coli E69 by binding to the transporter Wza163 | NA |
| Colanic acid | β-(1,4)-linked repeating heteropolymer of fucose, glucose, glucuronate and galactose, decorated with O-acetyl and pyruvate side chains | E. coli, Shigella spp., Salmonella spp. and Enterobacter spp. | Biofilm matrix component; stress tolerance; protection from antibiotic treatment | NA | NA |
| GBS polysaccharides | 9 serotypes, heteropolymer of glucose, galactose and N-acetylneuraminic acid; N-acetylglucosamine or rhamnose are variable | Group B Streptococcus (also known as Streptococcus agalactiae) | Capsular, antiphagocytic factor; interfering with complement-mediated killing | NA | Various capsular polysaccharides conjugated to carrier proteins are currently under investigation as vaccinesc |
| Polysialic acid capsular polysaccharides | Polymer of N-acetylneuraminic acid with (α2→8)-sialic acid linkages | Neisseria meningitidis and E. coli K1 | Capsule component; molecular mimicry with polysialic acid moieties of human tissue antigens; antiphagocytic factor | γ-Cyclodextrin blocks the Wza transporter163 | N. meningitidis serogroup A, C, Y and W-135 capsular polysaccharide or oligosaccharide antigens individually conjugated to DT, TT or CRM197; synthetic glycoconjugate of Hep2Kdo2 (the core tetrasaccharide in LPS) and DT164f |
| Pneumococcal polysaccharides | >91 serotypes; differ from each other by their sugar composition, their linkage between the sugars and their stereoisomeric forms | Streptococcus pneumonia (8 genetic groups due to variation in cps loci) | Capsule component; required for pathogen transition from the lung to the bloodstream; antiphagocytic factor | The glycoside hydrolase Pn3Pase degrades the type 3 capsular polysaccharide of S. pneumonia165 | Mixture of purified CPSs from multiple types of S. pneumonia; conjugate vaccines containing CPSs |
| Staphylococcus CPS | >10 serotypes; CP5 and CP8 serotypes have repeating units of N-acetyl mannosaminuronic acid, N-acetyl l-fucosamine and N-acetyl d-fucosamine; variable based on glycosidic linkages between the sugars and the sites of O-acetylation | Staphylococcus aureus | Capsule component; antiphagocytic factor | NA | CPS (that is, CP5 and CP8) conjugated to P. aeruginosa exotoxin Ac |
CPS, capsular polysaccharide; DT, diphtheria toxoid; LPS, lipopolysaccharide; mAb, monoclonal antibody; NA, not available; TT, tetanus toxoid. aLipopolysaccharides (for example, O antigen) are not included. bA complete list of glycoconjugate vaccines is provided in ref.166. cIn clinical trials. dPassive immunization. eSee EK3D database devoted to E. coli K antigens. fAntibacterial vaccination strategy.