Bacterial Polysaccharides Animal Pathogens Salmonella enteriditis E coli Neisseria meningitidis Haemophilus influenzae Proteus mirabilis Proteus vulgaris Mycobacteria many others Soil Bacteria Rhizobiaceae Pseudomonas solanacearum Erwinia amylovora many others Polysaccharides Extracellular polysaccharides EPSs Excreted heteropolysaccharides Most often acidic Frequently form solutions of high viscosity Gram positive and Gram negative products Capsular Polysaccharides CPSs Cell associated heteropolysaccharides Most often acidic but some are neutral Solutions can be highly viscous Gram positive and Gram negative products Lipopolysaccharides LPSs Component of the outer membrane Amphiphilic Gram negative bacterial component Teichoic acid Gram Positive Mycobacterium cell wall components Mycolyl arabinogalactan Lipooligosaccharides LOSs Glycopeptidolipids GPLs Phenolic glycolipids PGLs Polysaccharide Functions Prevention of desiccation Survival Adherence Colonization of oral surfaces Colonization of catheters Bacteria plant interactions Resistance to non specific host immunity Complement mediated phagocytosis Complement mediated killing Resistance to specific host immunity Poor antibody response Cell cell recognition signaling Bacteria plant interactions Gram Negative Bacterial Cell Wall EPS CPS Lipopolysaccharides Structure Synthesis Function READ Raetz and Whitfield 2002 Lipopolysaccharide Endotoxins Endotoxins Ann Rev Biochem Biochem 71 63571 635 700 LPS I LPS II Core Lipid A Core Lipid A Core Lipid A O Chain LPS III IV V O Chain Schematic Diagram of a Lipopolysaccharide Examples of Capsular Polysaccharides from Enteric Bacteria Group I 4 D GlcA 1 4 D GlcNAc 1 L Serine 6 amide 6 D GlcNAc 1 E coli K40 CPS Group II D GlcA 1 2 D Man 1 3 D Glc 3 3 D Gal 1 n E coli K30 CPS 8 Neu5Ac 2 9 Neu5Ac 2 E coli K92 CPS 3 D Rib 1 n 7 Kdo 2 n E coli K23 CPS Whitfield and Valvano 1993 Biosynthesis and expression of cellcell surface polysaccharides in gramgram negative bacteria Adv Microbial Physiol 35 13535 135 246 n E coli Capsular Polysaccharide E coli K30 wt E coli K30 CPS minus E coli K30 CPS LPS minus From Current Topics in Microbiology and Immunology 1990 Ed by K Jann and B Jann Virulence Functions of Bacterial Capsular and Lipopolysaccharides Pseudomonas aeroginosa Rocchetta Rocchetta Burrows and Lam 1999 Genetics of OO antigen biosynthesis in Pseudomonas aeruginosa Microbiol Microbiol and Molecular Biol Rev 63 52363 523 553 READ pages 523523 528 H HOOC H HOOC H O HO O OH HOOC H H OH O H H HO O HOOC H OH O H OH OH H O H H H H H O O H C H 3 O H OH HO H O HOH3C H H3C H O HO H O H H NHAc 3 D Rha 1 2 D Rha 1 3 D Rha 1 H H H OH H OH O11 B Band LPS O Polysaccharide H H O O NHAc H O H 3 L FucNAc 1 3 D FucNAc 1 2 D Glc 1 H R2 R2 4 D ManA 1 4 L GulA 1 H H OH O O Alginic Acid R2 HO HO H H H O HH HO H HO O H3C O H H H HO H A Band LPS O Polysaccharide OH H R2 H O H R2 H H R2 O OH Contributions of Pseudomonas aeroginosa Polysaccharides to Pathogenicity Mutant strains which can not produce an LPS O chain polysaccharide are much less infective and much more sensitive to serum killing than are wild type strains that have polysaccharide O chain defective mutants are bound more efficiently by a receptor on the surface of epithelial cells presumably resulting in greater ingestion and destruction of P aeroginosa by these cells B band polysaccharide is both immunogenic and able to confer serum resistance while A band polysaccharide is relatively non immunogenic and does not confer serum resistance Bacteria isolated from lungs of CF patients produce EPS alginic acid and LPS with A band but not B band polysaccharide Alginic acid is correlated with microcolony growth within the lungs which takes place on biofilm consisting of alginic acid Rocchetta Rocchetta Burrows and Lam 1999 Genetics and OO antigen biosynthesis in Pseudomonas aeroginosa Microbiol Microbiol and Mol Biol Rev 63 52363 523 553 Pathogenicity of Neisseria meningitidis 350 000 deaths year world wide Fatality rate in children is 20 fold greater than in adults In epidemics there is a shift to older children and adults 15 to 20 yearolds The organism is common in the mucous membranes Pathogenicity Attachment Piliated acapsular cells containing LPS with terminal Gal 1 4 Glc moiety that is not sialylated An outer membrane protein Opc mediates attachment Enzymes involved in sialylation of LOS and in production of sialic acidcontaining CPS are down regulated e g Lst or lgt cluster Attachment is followed by cell invasion multiplication and entry into the blood stream Invasive Cells Once in the blood stream sialylated LPS and CPS are produced CPS inhibits immune response LPS oligosaccharides mimic those of host glycosphingolipids Sialylated LPS structures contribute to serum resistance Release of LPS into the blood stream leads to endotoxemia Kahler and Stephens 1998 Genetic basis for biosynthesis structure and function of meningococcal lipooligosaccharide Endotoxin Crit Rev Microbiol 24 281 334 N Linked Glycoproteins Ganglioside Structures and Biosynthesis Gal Glc Cer CMPCMP SA CMP CMPCMP SA Gal Glc Cer SA UDPUDP GalNAc GM3 UDP GalNAc Gal Glc Cer GM2 SA UDPUDP Gal UDP CMP Gal Glc Cer SA UDPUDP GalNAc SA GD3 UDP CMPCMP SA GalNAc Gal Glc Cer GD2 SA UDPUDP Gal SA UDP Gal GalNAc Gal Glc Cer Gal GalNAc Gal Glc Cer SA GM1a SA GD1b CMPCMP SA CMPCMP SA SA CMP CMP CMP Gal Glc Cer SA UDPUDP GalNAc GT3 SA SA UDP GalNAc Gal Glc Cer SA GT2 UDPUDP Gal SA SA UDP Gal GalNAc Gal Glc Cer SA GT3 CMPCMP SA SA SA CMP Gal GalNAc Gal Glc Cer Gal GalNAc Gal Glc Cer Gal GalNAc Gal Glc Cer SA SA G SA SA G SA SA G T1b D1a Q1c SA SA SA a series b series c series Neisseria meningitidis NMB Kdo 2 Attachment Blood stream 4 NeuNAc 2 3 Gal 1 4 GlcNAc 1 3 Gal 1 4 Glc 1 4 Hep 1 5 Kdo 2 3 PEA Serum resistance NMB LOS 6 Glc 1 3 Hep 1 2 Mimicry Inhibits immune response GlcNAc 1 8 NeuNAc 2 NMB CPS n Attachment 6 GlcN 1 6 GlcN 1 P R RR NoRCPS Blood stream CPS Kahler and Stephens 1998 Genetic basis for biosynthesis structure and function of meningococcal lipooligosaccharide Endotoxin Endotoxin Crit Crit Rev Microbiol 24 281 24 281 334 Phase Variable Changes in Genes lgtA and lgtC within the lgtABCDE Operon of Neisseria gonorrhoeae Can Modulate Gonococcal Susceptibility to Normal Human Serum William Shafer Emory University Anup Datta Kumar Kolli Russell Carlson CCRC UGA LOS Ng NHS sensitive Host LOS Ng NHS resistant Regulation of Glycosyl Transferases by Slip Strand Mispairing Events Glycosyl