Review: Lipopolysaccharide biosynthesis in Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa causes serious nosocomial infections, and an important virulence factor produced by this organism is lipopolysaccharide (LPS). This review summarizes knowledge about biosynthesis of all three structural domains of LPS — lipid A, core oligosaccharide, and O polysaccharides. In addition, based on similarities with other bacterial species, this review proposes new hypothetical pathways for unstudied steps in the biosynthesis of P. aeruginosa LPS. Lipid A biosynthesis is discussed in relation to Escherichia coli and Salmonella, and the biosyntheses of core sugar precursors and core oligosaccharide are summarised. Pseudomonas aeruginosa attaches a Common Polysaccharide Antigen and O-Specific Antigen polysaccharides to lipid A-core. Both forms of O polysaccharide are discussed with respect to their independent synthesis mechanisms. Recent advances in understanding O-polysaccharide biosynthesis since the last major review on this subject, published nearly a decade ago, are highlighted. Since P. aeruginosa O polysaccharides contain unusual sugars, sugar-nucleotide biosynthesis pathways are reviewed in detail. Knowledge derived from detailed studies in the O5, O6 and O11 serotypes is applied to predict biosynthesis pathways of sugars in poorly-studied serotypes, especially O1, O4, and O13/O14. Although further work is required, a full understanding of LPS biosynthesis in P. aeruginosa is almost within reach.

Keywords

lipid A lipopolysaccharide O antigen core Pseudomonas aeruginosa

References

Villavicencio RT The history of blue pus. J Am Coll Surg 1998; 187: 212-216.

Cardo D. , Horan T. , Andrus M. et al. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004; 32: 470-485.

Govan JR , Deretic V. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol Rev 1996 ; 60: 539-574.

Lang AB , Horn MP , Imboden MA , Zuercher AW Prophylaxis and therapy of Pseudomonas aeruginosa infection in cystic fibrosis and immunocompromised patients. Vaccine 2004 ; 22 (Suppl 1): S44-S48.

Taneja N. , Emmanuel R. , Chari PS , Sharma M. A prospective study of hospital-acquired infections in burn patients at a tertiary care referral centre in North India. Burns 2004; 30: 665-669.

Lyczak JB , Cannon CL , Pier GB Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist. Microbes Infect 2000 ; 2: 1051-1060.

Poole K. Efflux-mediated multiresistance in Gram-negative bacteria. Clin Microbiol Infect 2004; 10: 12-26.

Yoshimura F. , Nikaido H. Permeability of Pseudomonas aeruginosa outer membrane to hydrophilic solutes. J Bacteriol 1982; 152: 636-642.

Nikaido H. , Hancock REW. Outer membrane permeability of Pseudomonas aeruginosa. In: Sokatch JR. (ed). The Bacteria, a Treatise on Structure and Function. Orlando, FL: Academic Press, 1986; 145-193.

10.

El’Garch F. , Jeannot K. , Hocquet D. , Llanes-Barakat C. , Plesiat P. Cumulative effects of several nonenzymatic mechanisms on the resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrob Agents Chemother 2007; 51: 1016-1021.

11.

Giamarellou H. Prescribing guidelines for severe Pseudomonas infections. J Antimicrob Chemother 2002; 49: 229-233.

12.

Foweraker J. Recent advances in the microbiology of respiratory tract infection in cystic fibrosis. Br Med Bull 2009; 89: 93-110.

13.

Rocchetta HL , Burrows LL , Lam JS Genetics of O-antigen biosynthesis in Pseudomonas aeruginosa. Microbiol Mol Biol Rev 1999; 63: 523-553.

14.

Stanislavsky ES , Lam JS Pseudomonas aeruginosa antigens as potential vaccines. FEMS Microbiol Rev 1997; 21: 243-277.

15.

Galanos C. , Lüderitz O. , Rietschel ET et al. Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities. Eur J Biochem 1985; 148: 1-5.

16.

Alexander C. , Rietschel ET Bacterial lipopolysaccharides and innate immunity. J Endotoxin Res 2001; 7: 167-202.

17.

Backhed F. , Normark S. , Schweda EK , Oscarson S. , Richter-Dahlfors A. Structural requirements for TLR4-mediated LPS signalling: a biological role for LPS modifications. Microbes Infect 2003 ; 5: 1057-1063.

18.

Hajjar AM , Ernst RK , Tsai JH , Wilson CB , Miller SI Human Toll-like receptor 4 recognizes host-specific LPS modifications . Nat Immunol 2002; 3: 354-359.

19.

Ernst RK , Hajjar AM , Tsai JH , Moskowitz SM , Wilson CB , Miller SI Pseudomonas aeruginosa lipid A diversity and its recognition by Toll-like receptor 4. J Endotoxin Res 2003; 9: 395-400.

20.

Hancock RE , Diamond G. The role of cationic antimicrobial peptides in innate host defences . Trends Microbiol 2000; 8: 402-410.

21.

Trent MS , Stead CM , Tran AX , Hankins JV Diversity of endotoxin and its impact on pathogenesis. J Endotoxin Res 2006; 12: 205-223.

22.

Ernst RK , Yi EC , Guo L. et al. Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa. Science 1999; 286: 1561-1565.

23.

McPhee JB , Lewenza S. , Hancock RE Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa. Mol Microbiol 2003; 50: 205-217.

24.

Pier GB , Grout M. , Zaidi TS , Goldberg JB How mutant CFTR may contribute to Pseudomonas aeruginosa infection in cystic fibrosis. Am J Respir Crit Care Med 1996; 154: S175-S182.

25.

Willcox MD Pseudomonas aeruginosa infection and inflammation during contact lens wear: a review. Optom Vis Sci 2007; 84: 273-278.

26.

Fleiszig SM , Zaidi TS , Fletcher EL , Preston MJ , Pier GB Pseudomonas aeruginosa invades corneal epithelial cells during experimental infection. Infect Immun 1994; 62: 3485-3493.

27.

Fleiszig SM , Zaidi TS , Pier GB Pseudomonas aeruginosa invasion of and multiplication within corneal epithelial cells in vitro. Infect Immun 1995; 63: 4072-4077.

28.

Zaidi TS , Fleiszig SM , Preston MJ , Goldberg JB , Pier GB Lipopolysaccharide outer core is a ligand for corneal cell binding and ingestion of Pseudomonas aeruginosa. Invest Ophthalmol Vis Sci 1996; 37: 976-986.

29.

Zaidi TS , Lyczak J. , Preston M. , Pier GB Cystic fibrosis transmembrane conductance regulator-mediated corneal epithelial cell ingestion of Pseudomonas aeruginosa is a key component in the pathogenesis of experimental murine keratitis. Infect Immun 1999; 67: 1481-1492.

30.

Pier GB , Grout M. , Zaidi TS Cystic fibrosis transmembrane conductance regulator is an epithelial cell receptor for clearance of Pseudomonas aeruginosa from the lung. Proc Natl Acad Sci USA 1997; 94: 12088-12093.

31.

Schroeder TH , Reiniger N. , Meluleni G. , Grout M. , Coleman FT , Pier GB Transgenic cystic fibrosis mice exhibit reduced early clearance of Pseudomonas aeruginosa from the respiratory tract. J Immunol 2001; 166: 7410-7418.

32.

Dasgupta T. , de Kievit TR , Masoud H. et al. Characterization of lipopolysaccharide-deficient mutants of Pseudomonas aeruginosa derived from serotypes O3, O5, and O6. Infect Immun 1994; 62: 809-817.

33.

Lam MY , McGroarty EJ , Kropinski AM et al. Occurrence of a common lipopolysaccharide antigen in standard and clinical strains of Pseudomonas aeruginosa. J Clin Microbiol 1989; 27: 962-967.

34.

Berry MC , McGhee GC , Zhao Y. , Sundin GW Effect of a waaL mutation on lipopolysaccharide composition, oxidative stress survival, and virulence in Erwinia amylovora. FEMS Microbiol Lett 2009; 291: 80-87.

35.

Abeyrathne PD , Daniels C. , Poon KK , Matewish MJ , Lam JS Functional characterization of WaaL, a ligase associated with linking O-antigen polysaccharide to the core of Pseudomonas aeruginosa lipopolysaccharide. J Bacteriol 2005; 187: 3002-3012.

36.

Hancock RE , Mutharia LM , Chan L. , Darveau RP , Speert DP , Pier GB Pseudomonas aeruginosa isolates from patients with cystic fibrosis: a class of serum-sensitive, nontypable strains deficient in lipopolysaccharide O side chains. Infect Immun 1983; 42: 170-177.

37.

Evans DJ , Pier GB , Coyne MJJr , Goldberg JB The rfb locus from Pseudomonas aeruginosa strain PA103 promotes the expression of O antigen by both LPS-rough and LPS-smooth isolates from cystic fibrosis patients. Mol Microbiol 1994; 13: 427-434.

38.

Kadurugamuwa JL , Lam JS , Beveridge TJ Interaction of gentamicin with the A band and B band lipopolysaccharides of Pseudomonas aeruginosa and its possible lethal effect. Antimicrob Agents Chemother 1993; 37: 715-721.

39.

Hatano K. , Goldberg JB , Pier GB Biologic activities of antibodies to the neutral-polysaccharide component of the Pseudomonas aeruginosa lipopolysaccharide are blocked by O side chains and mucoid exopolysaccharide (alginate). Infect Immun 1995; 63: 21-26.

40.

Matewish MJ The functional role of lipopolysaccharide in the cell envelope and surface proteins of Pseudomonas aeruginosa. PhD thesis. University of Guelph, Ontario , Canada, 2004 .

41.

Cryz SJJr , Pitt TL , Furer E. , Germanier R. Role of lipopolysaccharide in virulence of Pseudomonas aeruginosa. Infect Immun 1984; 44: 508-513.

42.

Priebe GP , Dean CR , Zaidi T. et al. The galU gene of Pseudomonas aeruginosa is required for corneal infection and efficient systemic spread following pneumonia but not for infection confined to the lung. Infect Immun 2004; 72: 4224-4232.

43.

Tang HB , DiMango E. , Bryan R. et al. Contribution of specific Pseudomonas aeruginosa virulence factors to pathogenesis of pneumonia in a neonatal mouse model of infection. Infect Immun 1996; 64: 37-43.

44.

Coyne MJJr , Russell KS , Coyle CL , Goldberg JB The Pseudomonas aeruginosa algC gene encodes phosphoglucomutase, required for the synthesis of a complete lipopolysaccharide core. J Bacteriol 1994; 176: 3500-3507.

45.

Knirel YA , Bystrova OV , Kocharova NA , Zähringer U. , Pier GB Conserved and variable structural features in the lipopolysaccharide of Pseudomonas aeruginosa. J Endotoxin Res 2006; 12: 324-336.

46.

Kulshin VA , Zähringer U. , Lindner B. , Jäger KE , Dmitriev BA , Rietschel ET Structural characterization of the lipid A component of Pseudomonas aeruginosa wild-type and rough mutant lipopolysaccharides. Eur J Biochem 1991; 198: 697-704.

47.

Ernst RK , Moskowitz SM , Emerson JC et al. Unique lipid A modifications in Pseudomonas aeruginosa isolated from the airways of patients with cystic fibrosis. J Infect Dis 2007; 196: 1088-1092.

48.

Bhat R. , Marx A. , Galanos C. , Conrad RS Structural studies of lipid A from Pseudomonas aeruginosa PAO1: occurrence of 4-amino-4-deoxyarabinose. J Bacteriol 1990 ; 172: 6631-6636.

49.

Moskowitz SM , Ernst RK , Miller SI PmrAB, a two-component regulatory system of Pseudomonas aeruginosa that modulates resistance to cationic antimicrobial peptides and addition of aminoarabinose to lipid A. J Bacteriol 2004; 186: 575-579.

50.

Raetz CR , Whitfield C. Lipopolysaccharide endotoxins. Annu Rev Biochem 2002; 71: 635-700.

51.

Trent MS Biosynthesis, transport, and modification of lipid A. Biochem Cell Biol 2004; 82: 71-86.

52.

Dotson GD , Kaltashov IA , Cotter RJ , Raetz CR Expression cloning of a Pseudomonas gene encoding a hydroxydecanoyl-acyl carrier protein-dependent UDP-GlcNAc acyltransferase. J Bacteriol 1998; 180: 330-337.

53.

Williamson JM , Anderson MS , Raetz CR Acyl-acyl carrier protein specificity of UDP-GlcNAc acyltransferases from Gram-negative bacteria: relationship to lipid A structure . J Bacteriol 1991; 173: 3591-3596.

54.

Wyckoff TJ , Lin S. , Cotter RJ , Dotson GD , Raetz CR Hydrocarbon rulers in UDP-N-acetylglucosamine acyltransferases. J Biol Chem 1998; 273: 32369-32372.

55.

Clementz T. , Bednarski JJ , Raetz CR Function of the htrB high temperature requirement gene of Escherichia coli in the acylation of lipid A: HtrB catalyzed incorporation of laurate. J Biol Chem 1996; 271: 12095-12102.

56.

Clementz T. , Zhou Z. , Raetz CR Function of the Escherichia coli msbB gene, a multicopy suppressor of htrB knockouts, in the acylation of lipid A. Acylation by MsbB follows laurate incorporation by HtrB. J Biol Chem 1997; 272: 10353-10360.

57.

Brozek KA , Raetz CR Biosynthesis of lipid A in Escherichia coli. Acyl carrier protein-dependent incorporation of laurate and myristate. J Biol Chem 1990; 265: 15410-15417.

58.

Goldman RC , Doran CC , Kadam SK , Capobianco JO Lipid A precursor from Pseudomonas aeruginosa is completely acylated prior to addition of 3-deoxy-D-manno-octulosonate. J Biol Chem 1988; 263: 5217-5223.

59.

Mohan S. , Raetz CR Endotoxin biosynthesis in Pseudomonas aeruginosa: enzymatic incorporation of laurate before 3-deoxy-D-manno-octulosonate. J Bacteriol 1994; 176: 6944-6951.

60.

Guo L. , Lim KB , Poduje CM et al. Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides. Cell 1998; 95: 189-198.

61.

Gibbons HS , Lin S. , Cotter RJ , Raetz CR Oxygen requirement for the biosynthesis of the S-2-hydroxymyristate moiety in Salmonella typhimurium lipid A. Function of LpxO, A new Fe2+/alpha-ketoglutarate-dependent dioxygenase homologue. J Biol Chem 2000; 275: 32940-32949.

62.

Gibbons HS , Reynolds CM , Guan Z. , Raetz CR An inner membrane dioxygenase that generates the 2-hydroxymyristate moiety of Salmonella lipid A. Biochemistry 2008; 47: 2814-2825.

63.

Gibbons HS , Kalb SR , Cotter RJ , Raetz CR Role of Mg2+ and pH in the modification of Salmonella lipid A after endocytosis by macrophage tumour cells. Mol Microbiol 2005; 55: 425-440.

64.

Trent MS , Pabich W. , Raetz CR , Miller SI A PhoP/PhoQ-induced lipase (PagL) that catalyzes 3-O-deacylation of lipid A precursors in membranes of Salmonella typhimurium. J Biol Chem 2001; 276: 9083-9092.

65.

Geurtsen J. , Steeghs L. , Hove JT , van der Ley P. , Tommassen J. Dissemination of lipid A deacylases (PagL) among Gram-negative bacteria: identification of active-site histidine and serine residues. J Biol Chem 2005; 280: 8248-8259.

66.

Ernst RK , Adams KN , Moskowitz SM et al. The Pseudomonas aeruginosa lipid A deacylase: selection for expression and loss within the cystic fibrosis airway. J Bacteriol 2006; 188: 191-201.

67.

Rutten L. , Geurtsen J. , Lambert W. et al. Crystal structure and catalytic mechanism of the LPS 3-O-deacylase PagL from Pseudomonas aeruginosa. Proc Natl Acad Sci USA 2006; 103: 7071-7076.

68.

Yan A. , Guan Z. , Raetz CR An undecaprenyl phosphate-aminoarabinose flippase required for polymyxin resistance in Escherichia coli. J Biol Chem 2007; 282: 36077-36089.

69.

Hung RJ , Chien HS , Lin RZ et al. Comparative analysis of two UDP-glucose dehydrogenases in Pseudomonas aeruginosa PAO1. J Biol Chem 2007; 282: 17738-17748.

70.

McPhee JB , Bains M. , Winsor G. et al. Contribution of the PhoPPhoQ and PmrA-PmrB two-component regulatory systems to Mg2+-induced gene regulation in Pseudomonas aeruginosa. J Bacteriol 2006; 188: 3995-4006.

71.

Nummila K. , Kilpelainen I. , Zähringer U. , Vaara M. , Helander IM Lipopolysaccharides of polymyxin B-resistant mutants of Escherichia coli are extensively substituted by 2-aminoethyl pyrophosphate and contain aminoarabinose in lipid A. Mol Microbiol 1995 ; 16: 271-278.

72.

Helander IM , Kato Y. , Kilpelainen I. et al. Characterization of lipopolysaccharides of polymyxin-resistant and polymyxin-sensitive Klebsiella pneumoniae O3. Eur J Biochem 1996; 237: 272-278.

73.

Gunn JS , Lim KB , Krueger J. et al. PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance. Mol Microbiol 1998; 27: 1171-1182.

74.

McCoy AJ , Liu H. , Falla TJ , Gunn JS Identification of Proteus mirabilis mutants with increased sensitivity to antimicrobial peptides . Antimicrob Agents Chemother 2001; 45: 2030-2037.

75.

Derzelle S. , Turlin E. , Duchaud E. et al. The PhoP-PhoQ two-component regulatory system of Photorhabdus luminescens is essential for virulence in insects. J Bacteriol 2004; 186: 1270-1279.

76.

Robey M. , O’Connell W. , Cianciotto NP Identification of Legionella pneumophila rcp, a pagP-like gene that confers resistance to cationic antimicrobial peptides and promotes intracellular infection . Infect Immun 2001; 69: 4276-4286.

77.

Preston A. , Maxim E. , Toland E. et al. Bordetella bronchiseptica PagP is a Bvg-regulated lipid A palmitoyl transferase that is required for persistent colonization of the mouse respiratory tract. Mol Microbiol 2003; 48: 725-736.

78.

Brozek KA , Bulawa CE , Raetz CR Biosynthesis of lipid A precursors in Escherichia coli. A membrane-bound enzyme that transfers a palmitoyl residue from a glycerophospholipid to lipid X. J Biol Chem 1987; 262: 5170-5179.

79.

Bishop RE , Gibbons HS , Guina T. , Trent MS , Miller SI , Raetz CR Transfer of palmitate from phospholipids to lipid A in outer membranes of Gram-negative bacteria. EMBO J 2000; 19: 5071-5080.

80.

El Hamidi A. , Novikov A. , Karibian D. , Perry MB , Caroff M. Structural characterization of Bordetella parapertussis lipid A. J Lipid Res 2009; 50: 854-859.

81.

MacArthur I. , Mann PB , Harvill ET , Preston A. IEIIS Meeting minireview: Bordetella evolution: lipid A and Toll-like receptor 4. J Endotoxin Res 2007; 13: 243-247.

82.

Walsh AG , Matewish MJ , Burrows LL , Monteiro MA , Perry MB , Lam JS Lipopolysaccharide core phosphates are required for viability and intrinsic drug resistance in Pseudomonas aeruginosa. Mol Microbiol 2000; 35: 718-727.

83.

Schnaitman CA , Klena JD Genetics of lipopolysaccharide biosynthesis in enteric bacteria. Microbiol Rev 1993; 57: 655-682.

84.

Eagon R. , Carson K. Lysis of cell walls and intact cells of Pseudomonas aeruginosa by ethylenediamine tetraacetic acid and by lysosozyme. Can J Microbiol 1965; 11: 193-201.

85.

Gray GW , Wilkinson SG The effect of ethylenediaminetetraacetic acid on the cell walls of some Gram-negative bacteria. J Gen Microbiol 1965; 39: 385-399.

86.

Wilkinson SG Cell walls of Pseudomonas species sensitive to ethylenediaminetetraacetic acid. J Bacteriol 1970; 104: 1035-1044.

87.

Sanchez Carballo PM , Rietschel ET , Kosma P. , Zähringer U. Elucidation of the structure of an alanine-lacking core tetrasaccharide trisphosphate from the lipopolysaccharide of Pseudomonas aeruginosa mutant H4. Eur J Biochem 1999; 261: 500-508.

88.

Knirel YA , Bystrova OV , Shashkov AS et al. Structural analysis of the lipopolysaccharide core of a rough, cystic fibrosis isolate of Pseudomonas aeruginosa. Eur J Biochem 2001; 268: 4708-4719.

89.

Bystrova OV , Shashkov AS , Kocharova NA et al. Structural studies on the core and the O-polysaccharide repeating unit of Pseudomonas aeruginosa immunotype 1 lipopolysaccharide. Eur J Biochem 2002; 269: 2194-2203.

90.

Kooistra O. , Bedoux G. , Brecker L. et al. Structure of a highly phosphorylated lipopolysaccharide core in the Delta algC mutants derived from Pseudomonas aeruginosa wild-type strains PAO1 (serogroup O5) and PAC1R (serogroup O3) . Carbohydr Res 2003; 338: 2667-2677.

91.

Beckmann F. , Moll H. , Jäger KE , Zähringer U. Preliminary communication 7-O-carbamoyl-L-glycero-D-manno-heptose: a new core constituent in the lipopolysaccharide of Pseudomonas aeruginosa. Carbohydr Res 1995 ; 267: C3-C7.

92.

Sadovskaya I. , Brisson JR , Lam JS , Richards JC , Altman E. Structural elucidation of the lipopolysaccharide core regions of the wild-type strain PAO1 and O-chain-deficient mutant strains AK1401 and AK1012 from Pseudomonas aeruginosa serotype O5. Eur J Biochem 1998; 255: 673-684.

93.

Sadovskaya I. , Brisson JR , Thibault P. , Richards JC , Lam JS , Altman E. Structural characterization of the outer core and the Ochain linkage region of lipopolysaccharide from Pseudomonas aeruginosa serotype O5. Eur J Biochem 2000; 267: 1640-1650.

94.

Bystrova OV , Knirel YA , Lindner B. et al. Structures of the core oligosaccharide and O-units in the R- and SR-type lipopolysaccharides of reference strains of Pseudomonas aeruginosa Oserogroups. FEMS Immunol Med Microbiol 2006; 46: 85-99.

95.

Bystrova OV , Lindner B. , Moll H. et al. Structure of the lipopolysaccharide of Pseudomonas aeruginosa O-12 with a randomly O-acetylated core region. Carbohydr Res 2003; 338: 1895-1905.

96.

Choudhury B. , Carlson RW , Goldberg JB The structure of the lipopolysaccharide from a galU mutant of Pseudomonas aeruginosa serogroup-O11 . Carbohydr Res 2005; 340: 2761-2772.

97.

Drewry DT , Gray GW , Wilkinson SG Low-molecular-weight solutes released during mild acid hydrolysis of the lipopolysaccharide of Pseudomonas aeruginosa. Biochem J 1972; 130: 289-295.

98.

Wilkinson SG 31P N.M.R. evidence for the presence of triphosphate residues in lipopolysaccharides from Pseudomonas aeruginosa. Biochem J 1981; 199: 833-835.

99.

Choudhury B. , Carlson RW , Goldberg JB Characterization of the lipopolysaccharide from a wbjE mutant of the serogroup O11 Pseudomonas aeruginosa strain, PA103 . Carbohydr Res 2008; 343: 238-248.

100.

Bystrova OV , Lindner B. , Moll H. et al. Structure of the biological repeating unit of the O-antigen of Pseudomonas aeruginosa immunotype 4 containing both 2-acetamido-2,6-dideoxy-D-glucose and 2-acetamido-2,6-dideoxy-D-galactose . Carbohydr Res 2003; 338: 1801-1806.

101.

de Kievit TR , Lam JS Monoclonal antibodies that distinguish inner core, outer core, and lipid A regions of Pseudomonas aeruginosa lipopolysaccharide . J Bacteriol 1994; 176: 7129-7139.

102.

Poon KK , Westman EL , Vinogradov E. , Jin S. , Lam JS Functional characterization of MigA and WapR: putative rhamnosyltransferases involved in outer core oligosaccharide biosynthesis of Pseudomonas aeruginosa . J Bacteriol 2008; 190: 1857-1865.

103.

Postma PW , Lengeler JW , Jacobson GR Phosphoenolpyruvate:carbohydrate phosphotransferase systems of bacteria . Microbiol Rev 1993; 57: 543-594.

104.

Temple L. , Cuskey SM , Perkins RE et al. Analysis of cloned structural and regulatory genes for carbohydrate utilization in Pseudomonas aeruginosa PAO. J Bacteriol 1990; 172: 6396-6402.

105.

Dean CR , Goldberg JB Pseudomonas aeruginosa galU is required for a complete lipopolysaccharide core and repairs a secondary mutation in a PA103 (serogroup O11) wbpM mutant . FEMS Microbiol Lett 2002; 210: 277-283.

106.

Giraud MF , Naismith JH The rhamnose pathway. Curr Opin Struct Biol 2000; 10: 687-696.

107.

Graninger M. , Nidetzky B. , Heinrichs DE , Whitfield C. , Messner P. Characterization of dTDP-4-dehydrorhamnose 3,5-epimerase and dTDP-4-dehydrorhamnose reductase, required for dTDP-L-rhamnose biosynthesis in Salmonella enterica serovar Typhimurium LT2. J Biol Chem 1999; 274: 25069-25077.

108.

Blankenfeldt W. , Asuncion M. , Lam JS , Naismith JH The structural basis of the catalytic mechanism and regulation of glucose-1-phosphate thymidylyltransferase (RmlA). EMBO J 2000; 19: 6652-6663.

109.

Blankenfeldt W. , Giraud MF , Leonard G. et al. The purification, crystallization and preliminary structural characterization of glucose-1-phosphate thymidylyltransferase (RmlA), the first enzyme of the dTDP-L-rhamnose synthesis pathway from Pseudomonas aeruginosa. Acta Crystallogr D Biol Crystallogr 2000; 56: 1501-1504.

110.

Charnock SJ , Davies GJ Structure of the nucleotide-diphospho-sugar transferase, SpsA from Bacillus subtilis, in native and nucleotide-complexed forms. Biochemistry 1999; 38: 6380-6385.

111.

Melo A. , Glaser L. The nucleotide specificity and feedback control of thymidine diphosphate D-glucose pyrophosphorylase. J Biol Chem 1965 ; 240: 398-405.

112.

Dong C. , Major LL , Srikannathasan V. et al. RmlC, a C3′ and C5′ carbohydrate epimerase, appears to operate via an intermediate with an unusual twist boat conformation. J Mol Biol 2007; 365: 146-159.

113.

Rahim R. , Burrows LL , Monteiro MA , Perry MB , Lam JS Involvement of the rml locus in core oligosaccharide and O polysaccharide assembly in Pseudomonas aeruginosa. Microbiology 2000; 146 (Pt 11): 2803-2814.

114.

Raetz CR Biochemistry of endotoxins. Annu Rev Biochem 1990; 59: 129-170.

115.

Walsh AG , Burrows LL , Lam JS Genetic and biochemical characterization of an operon involved in the biosynthesis of 3-deoxy-D-manno-octulosonic acid in Pseudomonas aeruginosa . FEMS Microbiol Lett 1999; 173: 27-33.

116.

Lebioda L. , Stec B. Crystal structure of enolase indicates that enolase and pyruvate kinase evolved from a common ancestor. Nature 1988; 333: 683-686.

117.

Weng M. , Makaroff CA , Zalkin H. Nucleotide sequence of Escherichia coli pyrG encoding CTP synthetase . J Biol Chem 1986; 261: 5568-5574.

118.

Ray PH , Benedict CD , Grasmuk H. Purification and characterization of cytidine 5′-triphosphate:cytidine 5′-monophosphate-3deoxy-D-manno-octulosonate cytidylyltransferase. J Bacteriol 1981; 145: 1273-1280.

119.

Gronow S. , Oertelt C. , Ervela E. et al. Characterization of the physiological substrate for lipopolysaccharide heptosyltransferases I and II. J Endotoxin Res 2001; 7: 263-270.

120.

Eidels L. , Osborn MJ Lipopolysaccharide and aldoheptose biosynthesis in transketolase mutants of Salmonella typhimurium. Proc Natl Acad Sci USA 1971; 68: 1673-1677.

121.

Valvano MA , Marolda CL , Bittner M. , Glaskin-Clay M. , Simon TL , Klena JD The rfaE gene from Escherichia coli encodes a bifunctional protein involved in biosynthesis of the lipopolysaccharide core precursor ADP-L-glycero-D-mannoheptose . J Bacteriol 2000; 182: 488-497.

122.

Valvano MA , Messner P. , Kosma P. Novel pathways for biosynthesis of nucleotide-activated glycero-manno-heptose precursors of bacterial glycoproteins and cell surface polysaccharides. Microbiology 2002; 148: 1979-1989.

123.

Cantarel BL , Coutinho PM , Rancurel C. , Bernard T. , Lombard V. , Henrissat B. The Carbohydrate-Active EnZymes database (CAZy): an expert resource for glycogenomics. Nucleic Acids Res 2009; 37: D233-D238.

124.

Flint J. , Taylor E. , Yang M. et al. Structural dissection and high-throughput screening of mannosylglycerate synthase. Nat Struct Mol Biol 2005; 12: 608-614.

125.

Belunis CJ , Raetz CR Biosynthesis of endotoxins. Purification and catalytic properties of 3-deoxy-D-manno-octulosonic acid transferase from Escherichia coli. J Biol Chem 1992; 267: 9988-9997.

126.

Pradel E. , Parker CT , Schnaitman CA Structures of the rfaB, rfaI, rfaJ, and rfaS genes of Escherichia coli K-12 and their roles in assembly of the lipopolysaccharide core. J Bacteriol 1992; 174: 4736-4745.

127.

Hirokawa T. , Boon-Chieng S. , Mitaku S. SOSUI: classification and secondary structure prediction system for membrane proteins. Bioinformatics 1998; 14: 378-379.

128.

Krogh A. , Larsson B. , von Heijne G. , Sonnhammer EL Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 2001; 305: 567-580.

129.

Roantree RJ , Kuo TT , MacPhee DG The effect of defined lipopolysaccharide core defects upon antibiotic resistances of Salmonella typhimurium. J Gen Microbiol 1977; 103: 223-234.

130.

Chatterjee AK , Sanderson KE , Ross H. Influence of temperature on growth of lipopolysaccharide-deficient (rough) mutants of Salmonella typhimurium and Salmonella minnesota. Can J Microbiol 1976; 22: 1540-1548.

131.

de Kievit TR , Lam JS Isolation and characterization of two genes, waaC (rfaC) and waaF (rfaF), involved in Pseudomonas aeruginosa serotype O5 inner-core biosynthesis. J Bacteriol 1997; 179: 3451-3457.

132.

Yethon JA , Vinogradov E. , Perry MB , Whitfield C. Mutation of the lipopolysaccharide core glycosyltransferase encoded by waaG destabilizes the outer membrane of Escherichia coli by interfering with core phosphorylation. J Bacteriol 2000 ; 182: 5620-5623.

133.

Knirel YA , Helbig JH , Zähringer U. Structure of a decasaccharide isolated by mild acid degradation and dephosphorylation of the lipopolysaccharide of Pseudomonas fluorescens strain ATCC 49271. Carbohydr Res 1996; 283: 129-139.

134.

Leone S. , Izzo V. , Silipo A. et al. A novel type of highly negatively charged lipooligosaccharide from Pseudomonas stutzeri OX1 possessing two 4,6-O-(1-carboxy)-ethylidene residues in the outer core region. Eur J Biochem 2004 ; 271: 2691-2704.

135.

Zdorovenko EL , Vinogradov E. , Zdorovenko GM et al. Structure of the core oligosaccharide of a rough-type lipopolysaccharide of Pseudomonas syringae pv. phaseolicola . Eur J Biochem 2004; 271: 4968-4977.

136.

Frirdich E. , Vinogradov E. , Whitfield C. Biosynthesis of a novel 3-deoxy-D-manno-oct-2-ulosonic acid-containing outer core oligosaccharide in the lipopolysaccharide of Klebsiella pneumoniae. J Biol Chem 2004; 279: 27928-27940.

137.

Regué M. , Izquierdo L. , Fresno S. et al. The incorporation of glucosamine into enterobacterial core lipopolysaccharide: two enzymatic steps are required . J Biol Chem 2005; 280: 36648-36656.

138.

Yang H. , Matewish M. , Loubens I. , Storey DG , Lam JS , Jin S. migA, a quorum-responsive gene of Pseudomonas aeruginosa, is highly expressed in the cystic fibrosis lung environment and modifies low-molecular-mass lipopolysaccharide . Microbiology 2000; 146: 2509-2519.

139.

Wang J. , Lory S. , Ramphal R. , Jin S. Isolation and characterization of Pseudomonas aeruginosa genes inducible by respiratory mucus derived from cystic fibrosis patients. Mol Microbiol 1996; 22: 1005-1012.

140.

Zhao X. , Lam JS WaaP of Pseudomonas aeruginosa is a novel eukaryotic type protein-tyrosine kinase as well as a sugar kinase essential for the biosynthesis of core lipopolysaccharide . J Biol Chem 2002; 277: 4722-4730.

141.

Zhao X. , Wenzel CQ , Lam JS Nonradiolabeling assay for WaaP, an essential sugar kinase involved in biosynthesis of core lipopolysaccharide of Pseudomonas aeruginosa. Antimicrob Agents Chemother 2002; 46: 2035-2037.

142.

To T. Purification and characterization of WapP of Pseudomonas aeruginosa, a putative lipopolysaccharide kinase. MSc thesis. University of Guelph , Ontario, Canada, 2006 .

143.

Coque JJ , Perez-Llarena FJ , Enguita FJ , Fuente JL , Martin JF , Liras P. Characterization of the cmcH genes of Nocardia lactamdurans and Streptomyces clavuligerus encoding a functional 3-hydroxymethylcephem O-carbamoyltransferase for cephamycin biosynthesis. Gene 1995; 162: 21-27.

144.

Scheeff ED , Bourne PE Structural evolution of the protein kinase-like superfamily. PLoS Comput Biol 2005; 1: e49.

145.

Tian Y. , Jackson P. , Gunter C. , Wang J. , Rock CO , Jackowski S. Placental thrombosis and spontaneous fetal death in mice deficient in ethanolamine kinase 2. J Biol Chem 2006 ; 281: 28438-28449.

146.

Brodsky IE , Ghori N. , Falkow S. , Monack D. Mig-14 is an inner membrane-associated protein that promotes Salmonella typhimurium resistance to CRAMP, survival within activated macrophages and persistent infection. Mol Microbiol 2005; 55: 954-972.

147.

Hasin M. , Kennedy EP Role of phosphatidylethanolamine in the biosynthesis of pyrophosphoethanolamine residues in the lipopolysaccharide of Escherichia coli. J Biol Chem 1982; 257: 12475-12477.

148.

Tamayo R. , Choudhury B. , Septer A. , Merighi M. , Carlson R. , Gunn JS Identification of cptA, a PmrA-regulated locus required for phosphoethanolamine modification of the Salmonella enterica serovar Typhimurium lipopolysaccharide core. J Bacteriol 2005; 187: 3391-3399.

149.

Cox AD , Li J. , Richards JC Identification and localization of glycine in the inner core lipopolysaccharide of Neisseria meningitidis. Eur J Biochem 2002; 269: 4169-4175.

150.

Lundström SL , Li J. , Deadman ME , Hood DW , Moxon ER , Schweda EK Structural analysis of the lipopolysaccharide from nontypeable Haemophilus influenzae strain R2846 . Biochemistry 2008; 47: 6025-6038.

151.

Molinaro A. , Silipo A. , Castro CD et al. Full structural characterization of Shigella flexneri M90T serotype 5 wild-type R-LPS and its delta galU mutant: glycine residue location in the inner core of the lipopolysaccharide. Glycobiology 2008; 18: 260-269.

152.

Gamian A. , Krzyzaniak A. , Barciszewska MZ , Gawronska I. , Barciszewski J. Specific incorporation of glycine into bacterial lipopolysaccharide. Novel function of specific transfer ribonucleic acids. Nucleic Acids Res 1991; 19: 6021-6025.

153.

Fox KL , Yildirim HH , Deadman ME , Schweda EK , Moxon ER , Hood DW Novel lipopolysaccharide biosynthetic genes containing tetranucleotide repeats in Haemophilus influenzae, identification of a gene for adding O-acetyl groups . Mol Microbiol 2005; 58: 207-216.

154.

Doerrler WT , Gibbons HS , Raetz CR MsbA-dependent translocation of lipids across the inner membrane of Escherichia coli. J Biol Chem 2004; 279: 45102-45109.

155.

Mamat U. , Meredith TC , Aggarwal P. et al. Single amino acid substitutions in either YhjD or MsbA confer viability to 3-deoxy-D-manno-oct-2-ulosonic acid-depleted Escherichia coli. Mol Microbiol 2008; 67: 633-648.

156.

Ghanei H. , Abeyrathne PD , Lam JS Biochemical characterization of MsbA from Pseudomonas aeruginosa. J Biol Chem 2007; 282: 26939-26947.

157.

Liu PV , Matsumoto H. , Kusama H. , Bergan TOM. Survey of heat-stable, major somatic antigens of Pseudomonas aeruginosa. Int J Syst Bacteriol 1983; 33: 256-264.

158.

Liu PV , Wang S. Three new major somatic antigens of Pseudomonas aeruginosa. J Clin Microbiol 1990; 28: 922-925.

159.

Akatova NS , Smirnova NE [Serological classification of Pseudomonas aeruginosa]. Zh Mikrobiol Epidemiol Immunobiol 1982; 87-91.

160.

Lànyi B. , Bergan T. Serological characterization of Pseudomonas aeruginosa. Methods Microbiol 1978; 10: 93-168.

161.

Raymond CK , Sims EH , Kas A. et al. Genetic variation at the O-antigen biosynthetic locus in Pseudomonas aeruginosa. J Bacteriol 2002; 184: 3614-3622.

162.

Rivera M. , Bryan LE , Hancock RE , McGroarty EJ Heterogeneity of lipopolysaccharides from Pseudomonas aeruginosa: analysis of lipopolysaccharide chain length. J Bacteriol 1988; 170: 512-521.

163.

de Kievit TR , Dasgupta T. , Schweizer H. , Lam JS Molecular cloning and characterization of the rfc gene of Pseudomonas aeruginosa (serotype O5). Mol Microbiol 1995; 16: 565-574.

164.

Rocchetta HL , Lam JS Identification and functional characterization of an ABC transport system involved in polysaccharide export of A-band lipopolysaccharide in Pseudomonas aeruginosa. J Bacteriol 1997 ; 179: 4713-4724.

165.

Whitfield C. Biosynthesis of lipopolysaccharide O antigens . Trends Microbiol 1995; 3: 178-185.

166.

Jiang XM , Neal B. , Santiago F. , Lee SJ , Romana LK , Reeves PR Structure and sequence of the rfb (O antigen) gene cluster of Salmonella serovar Typhimurium (strain LT2). Mol Microbiol 1991 ; 5: 695-713.

167.

Alexander DC , Valvano MA Role of the rfe gene in the biosynthesis of the Escherichia coli O7-specific lipopolysaccharide and other O-specific polysaccharides containing N-acetylglucosamine. J Bacteriol 1994; 176: 7079-7084.

168.

Zhang L. , Radziejewska-Lebrecht J. , Krajewska-Pietrasik D. , Toivanen P. , Skurnik M. Molecular and chemical characterization of the lipopolysaccharide O antigen and its role in the virulence of Yersinia enterocolitica serotype O:8. Mol Microbiol 1997; 23: 63-76.

169.

Bélanger M. , Burrows LL , Lam JS Functional analysis of genes responsible for the synthesis of the B-band O antigen of Pseudomonas aeruginosa serotype O6 lipopolysaccharide. Microbiology 1999; 145: 3505-3521.

170.

Rocchetta HL , Burrows LL , Pacan JC , Lam JS Three rhamnosyltransferases responsible for assembly of the A-band D-rhamnan polysaccharide in Pseudomonas aeruginosa: a fourth transferase, WbpL, is required for the initiation of both A-band and B-band lipopolysaccharide synthesis. Mol Microbiol 1998; 28: 1103-1119.

171.

Arsenault TL , Hughes DW , MacLean DB , Szarek WA , Kropinski AMB , Lam JS Structural studies on the polysaccharide portion of ‘A-band’ lipopolysaccharide from a mutant (AK14O1) of Pseudomonas aeruginosa PAO1. Can J Chem 1991; 69: 1273-1280.

172.

Vinogradov E. , Frirdich E. , MacLean LL et al. Structures of lipopolysaccharides from Klebsiella pneumoniae. Elucidation of the structure of the linkage region between core and polysaccharide O chain and identification of the residues at the nonreducing termini of the O chains. J Biol Chem 2002; 277: 25070-25081.

173.

Jann K. , Goldemann G. , Weisgerber C. , Wolf-Ullisch C. , Kanegasaki S. Biosynthesis of the O9 antigen of Escherichia coli. Initial reaction and overall mechanism. Eur J Biochem 1982; 127: 157-164.

174.

Weisgerber C. , Jann K. Glucosyldiphosphoundecaprenol, the mannose acceptor in the synthesis of the O9 antigen of Escherichia coli. Biosynthesis and characterization. Eur J Biochem 1982; 127: 165-168.

175.

Meier-Dieter U. , Barr K. , Starman R. , Hatch L. , Rick PD Nucleotide sequence of the Escherichia coli rfe gene involved in the synthesis of enterobacterial common antigen. Molecular cloning of the rfe-rff gene cluster. J Biol Chem 1992; 267: 746-753.

176.

Rick PD , Hubbard GL , Barr K. Role of the rfe gene in the synthesis of the O8 antigen in Escherichia coli K-12. J Bacteriol 1994; 176: 2877-2884.

177.

Yokota S. , Kaya S. , Kawamura T. , Araki Y. , Ito E. The structure of the O-specific chain of lipopolysaccharide from Pseudomonas aeruginosa IID 1008 (ATCC 27584). J Biochem 1986; 99: 1551-1561.

178.

Rocchetta HL , Pacan JC , Lam JS Synthesis of the A-band polysaccharide sugar D-rhamnose requires Rmd and WbpW: identification of multiple AlgA homologues, WbpW and ORF488, in Pseudomonas aeruginosa. Mol Microbiol 1998; 29: 1419-1434.

179.

Lightfoot J. , Lam JS Molecular cloning of genes involved with expression of A-band lipopolysaccharide, an antigenically conserved form, in Pseudomonas aeruginosa. J Bacteriol 1991 ; 173: 5624-5630.

180.

Shinabarger D. , Berry A. , May TB , Rothmel R. , Fialho A. , Chakrabarty AM Purification and characterization of phosphomannose isomerase-guanosine diphospho-D-mannose pyrophosphorylase. A bifunctional enzyme in the alginate biosynthetic pathway of Pseudomonas aeruginosa. J Biol Chem 1991 ; 266: 2080-2088.

181.

Remminghorst U. , Rehm BH Bacterial alginates: from biosynthesis to applications. Biotechnol Lett 2006; 28: 1701-1712.

182.

Lee HJ , Chang HY , Venkatesan N. , Peng HL Identification of amino acid residues important for the phosphomannose isomerase activity of PslB in Pseudomonas aeruginosa PAO1. FEBS Lett 2008; 582: 3479-3483.

183.

Ma L. , Lu H. , Sprinkle A. , Parsek MR , Wozniak DJ Pseudomonas aeruginosa Psl is a galactose- and mannose-rich exopolysaccharide . J Bacteriol 2007; 189: 8353-8356.

184.

Zielinski NA , Chakrabarty AM , Berry A. Characterization and regulation of the Pseudomonas aeruginosa algC gene encoding phosphomannomutase. J Biol Chem 1991; 266: 9754-9763.

185.

Olvera C. , Goldberg JB , Sanchez R. , Soberon-Chavez G. The Pseudomonas aeruginosa algC gene product participates in rhamnolipid biosynthesis . FEMS Microbiol Lett 1999; 179: 85-90.

186.

Lightfoot J. , Lam JS Chromosomal mapping, expression and synthesis of lipopolysaccharide in Pseudomonas aeruginosa: a role for guanosine diphospho (GDP)-D-mannose. Mol Microbiol 1993; 8: 771-782.

187.

King JD , Poon KK , Webb NA et al. The structural basis for catalytic function of GMD and RMD, two closely related enzymes from the GDP-D-rhamnose biosynthesis pathway. FEBS J 2009; 276: 2688-2700.

188.

Webb NA , Mulichak AM , Lam JS , Rocchetta HL , Garavito RM Crystal structure of a tetrameric GDP-D-mannose 4,6-dehydratase from a bacterial GDP-D-rhamnose biosynthetic pathway. Protein Sci 2004; 13: 529-539.

189.

Kido N. , Torgov VI , Sugiyama T. et al. Expression of the O9 polysaccharide of Escherichia coli: sequencing of the E. coli O9 rfb gene cluster, characterization of mannosyl transferases, and evidence for an ATP-binding cassette transport system. J Bacteriol 1995; 177: 2178-2187.

190.

Kido N. , Morooka N. , Paeng N. et al. Production of monoclonal antibody discriminating serological difference in Escherichia coli O9 and O9a polysaccharides. Microbiol Immunol 1997; 41: 519-525.

191.

Kido N. , Sugiyama T. , Yokochi T. , Kobayashi H. , Okawa Y. Synthesis of Escherichia coli O9a polysaccharide requires the participation of two domains of WbdA, a mannosyltransferase encoded within the wb* gene cluster. Mol Microbiol 1998; 27: 1213-1221.

192.

Cuthbertson L. , Kimber MS , Whitfield C. Substrate binding by a bacterial ABC transporter involved in polysaccharide export. Proc Natl Acad Sci USA 2007; 104: 19529-19534.

193.

Cuthbertson L. , Powers J. , Whitfield C. The C-terminal domain of the nucleotide-binding domain protein Wzt determines substrate specificity in the ATP-binding cassette transporter for the lipopolysaccharide O-antigens in Escherichia coli serotypes O8 and O9a. J Biol Chem 2005; 280: 30310-30319.

194.

Clarke BR , Cuthbertson L. , Whitfield C. Nonreducing terminal modifications determine the chain length of polymannose O antigens of Escherichia coli and couple chain termination to polymer export via an ATP-binding cassette transporter. J Biol Chem 2004; 279: 35709-35718.

195.

Schäffer C. , Wugeditsch T. , Kählig H. , Scheberl A. , Zayni S. , Messner P. The surface layer (S-layer) glycoprotein of Geobacillus stearothermophilus NRS 2004/3a. Analysis of its glycosylation . J Biol Chem 2002; 277: 6230-6239.

196.

Steiner K. , Novotny R. , Werz DB et al. Molecular basis of S-layer glycoprotein glycan biosynthesis in Geobacillus stearothermophilus . J Biol Chem 2008; 283: 21120-21133.

197.

King JD Characterisation of polysaccharide biosynthesis genes in Bordetella bronchiseptica . PhD thesis. University of Cambridge, UK, 2006.

198.

Preston A. , Petersen BO , Duus JO et al. Complete structures of Bordetella bronchiseptica and Bordetella parapertussis lipopolysaccharides . J Biol Chem 2006; 281: 18135-18144.

199.

Bera A. , Herbert S. , Jakob A. , Vollmer W. , Götz F. Why are pathogenic Staphylococci so lysozyme resistant? The peptidoglycan O-acetyltransferase OatA is the major determinant for lysozyme resistance of Staphylococcus aureus. Mol Microbiol 2005 ; 55: 778-787.

200.

Currie HL , Lightfoot J. , Lam JS Prevalence of gca, a gene involved in synthesis of A-band common antigen polysaccharide in Pseudomonas aeruginosa. Clin Diagn Lab Immunol 1995; 2: 554-562.

201.

Benson DA , Karsch-Mizrachi I. , Lipman DJ , Ostell J. , Wheeler DL GenBank. Nucleic Acids Res 2005; 33: D34-D38.

202.

Burrows LL , Charter DF , Lam JS Molecular characterization of the Pseudomonas aeruginosa serotype O5 (PAO1) B-band lipopolysaccharide gene cluster. Mol Microbiol 1996; 22: 481-495.

203.

Dean CR , Franklund CV , Retief JD et al. Characterization of the serogroup O11 O-antigen locus of Pseudomonas aeruginosa PA103. J Bacteriol 1999; 181: 4275-4284.

204.

Dean CR , Goldberg JB The wbpM gene in Pseudomonas aeruginosa serogroup O17 resides on a cryptic copy of the serogroup O11 O antigen gene locus. FEMS Microbiol Lett 2000; 187: 59-63.

205.

Burrows LL , Urbanic RV , Lam JS Functional conservation of the polysaccharide biosynthetic protein WbpM and its homologues in Pseudomonas aeruginosa and other medically significant bacteria. Infect Immun 2000; 68: 931-936.

206.

DiGiandomenico A. , Matewish MJ , Bisaillon A. , Stehle JR , Lam JS , Castric P. Glycosylation of Pseudomonas aeruginosa 1244 pilin: glycan substrate specificity. Mol Microbiol 2002; 46: 519-530.

207.

Miller WL , Lam JS Molecular biology of cell-surface polysaccharides in Pseudomonas aeruginosa: from gene to protein function. In: Cornelis P. (ed) Pseudomonas: Genomics and Molecular Biology. Horizon Scientific Press, 2007, 87-128.

208.

Creuzenet C. , Urbanic RV , Lam JS Structure-function studies of two novel UDP-GlcNAc C6 dehydratases/C4 reductases. Variation from the SYK dogma. J Biol Chem 2002; 277: 26769-26778.

209.

Creuzenet C. , Lam JS Topological and functional characterization of WbpM, an inner membrane UDP-GlcNAc C6 dehydratase essential for lipopolysaccharide biosynthesis in Pseudomonas aeruginosa. Mol Microbiol 2001; 41: 1295-1310.

210.

Schoenhofen IC , McNally DJ , Vinogradov E. et al. Functional characterization of dehydratase/aminotransferase pairs from Helicobacter and Campylobacter: enzymes distinguishing the pseudaminic acid and bacillosamine biosynthetic pathways. J Biol Chem 2006; 281: 723-732.

211.

Schoenhofen IC , McNally DJ , Brisson JR , Logan SM Elucidation of the CMP-pseudaminic acid pathway in Helicobacter pylori: synthesis from UDP-N-acetylglucosamine by a single enzymatic reaction. Glycobiology 2006; 16: 8C-14C.

212.

McNally DJ , Schoenhofen IC , Mulrooney EF et al. Identification of labile UDP-ketosugars in Helicobacter pylori, Campylobacter jejuni and Pseudomonas aeruginosa: key metabolites used to make glycan virulence factors . Chembiochem 2006; 7: 1865-1868.

213.

Ishiyama N. , Creuzenet C. , Miller WL et al. Structural studies of FlaA1 from Helicobacter pylori reveal the mechanism for inverting 4,6-dehydratase activity. J Biol Chem 2006; 281: 24489-24495.

214.

Morrison JP , Schoenhofen IC , Tanner ME Mechanistic studies on PseB of pseudaminic acid biosynthesis: a UDP-N-acetylglucosamine 5-inverting 4,6-dehydratase. Bioorg Chem 2008; 36: 312-320.

215.

Holloway BW , Cooper GN Lysogenic conversion in Pseudomonas aeruginosa . J Bacteriol 1962; 84: 1321-1324.

216.

Stover CK , Pham XQ , Erwin AL et al. Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature 2000; 406: 959-964.

217.

Knirel YA , Kochetkov NK The structure of lipopolysaccharides of Gram-negative bacteria. III. The structure of O-antigens: a review. Biochemistry 1994 ; 59: 1325-1382.

218.

Burrows LL , Pigeon KE , Lam JS Pseudomonas aeruginosa B-band lipopolysaccharide genes wbpA and wbpI and their Escherichia coli homologues wecC and wecB are not functionally interchangeable . FEMS Microbiol Lett 2000; 189: 135-141.

219.

Wenzel CQ , Daniels C. , Keates RA , Brewer D. , Lam JS Evidence that WbpD is an N-acetyltransferase belonging to the hexapeptide acyltransferase superfamily and an important protein for Oantigen biosynthesis in Pseudomonas aeruginosa PAO1. Mol Microbiol 2005; 57: 1288-1303.

220.

Westman EL , Preston A. , Field RA , Lam JS Biosynthesis of a rare di-N-acetylated sugar in the lipopolysaccharides of both Pseudomonas aeruginosa and Bordetella pertussis occurs via an identical scheme despite different gene clusters. J Bacteriol 2008; 190: 6060-6069.

221.

Miller WL , Wenzel CQ , Daniels C. , Larocque S. , Brisson JR , Lam JS Biochemical characterization of WbpA, a UDP-N-acetyl-D-glucosamine 6-dehydrogenase involved in O-antigen biosynthesis in Pseudomonas aeruginosa PAO1. J Biol Chem 2004; 279: 37551-37558.

222.

Sweet CR , Ribeiro AA , Raetz CR Oxidation and transamination of the 3′-position of UDP-N-acetylglucosamine by enzymes from Acidithiobacillus ferrooxidans. Role in the formation of lipid A molecules with four amide-linked acyl chains. J Biol Chem 2004; 279: 25400-25410.

223.

Westman EL , McNally DJ , Charchoglyan A. , Brewer D. , Field RA , Lam JS Characterization of WbpB, WbpE, and WbpD, and reconstitution of a pathway for the biosynthesis of UDP-2,3-diacetamido-2,3-dideoxy-D-mannuronic acid in Pseudomonas aeruginosa . J Biol Chem 2009; 284: 11854-11862.

224.

Larkin A. , Imperiali B. Biosynthesis of UDP-GlcNAc(3NAc)A by WbpB, WbpE, and WbpD: Enzymes in the Wbp Pathway Responsible for O-antigen Assembly in Pseudomonas aeruginosa PAO1 . Biochemistry 2009: In press.

225.

Westman EL , McNally DJ , Rejzek M. et al. Identification and biochemical characterization of two novel UDP-2,3-diacetamido-2,3-dideoxy-alpha-D-glucuronic acid 2-epimerases from respiratory pathogens. Biochem J 2007 ; 405: 123-130.

226.

King JD , Mulrooney EF , Vinogradov E. , Kneidinger B. , Mead K. , Lam JS lfnA from Pseudomonas aeruginosa O12 and wbuX from Escherichia coli O145 encode membrane-associated proteins and are required for expression of 2,6-dideoxy-2acetamidino-L-galactose in lipopolysaccharide O antigen. J Bacteriol 2008; 190: 1671-1679.

227.

McNally DJ , Hui JP , Aubry AJ et al. Functional characterization of the flagellar glycosylation locus in Campylobacter jejuni 81- 176 using a focused metabolomics approach. J Biol Chem 2006; 281: 18489-18498.

228.

Forsberg LS , Noel KD , Box J. , Carlson RW Genetic locus and structural characterization of the biochemical defect in the Oantigenic polysaccharide of the symbiotically deficient Rhizobium etli mutant, CE166. Replacement of N-acetylquinovosamine with its hexosyl-4-ulose precursor. J Biol Chem 2003; 278: 51347-51359.

229.

Zhao X. , Creuzenet C. , Belanger M. , Egbosimba E. , Li J. , Lam JS WbpO, a UDP-N-acetyl-D-galactosamine dehydrogenase from Pseudomonas aeruginosa serotype O6. J Biol Chem 2000; 275: 33252-33259.

230.

Miller WL , Matewish MJ , McNally DJ et al. Flagellin glycosylation in Pseudomonas aeruginosa PAK requires the O-antigen biosynthesis enzyme WbpO. J Biol Chem 2008; 283: 3507-3518.

231.

Ishiyama N. , Creuzenet C. , Lam JS , Berghuis AM Crystal structure of WbpP, a genuine UDP-N-acetylglucosamine 4-epimerase from Pseudomonas aeruginosa: substrate specificity in UDP-hexose 4-epimerases. J Biol Chem 2004; 279: 22635-22642.

232.

Creuzenet C. , Bélanger M. , Wakarchuk WW , Lam JS Expression, purification, and biochemical characterization of WbpP, a new UDP-GlcNAc C4 epimerase from Pseudomonas aeruginosa serotype O6. J Biol Chem 2000; 275: 19060-19067.

233.

Demendi M. , Ishiyama N. , Lam JS , Berghuis AM , Creuzenet C. Towards a better understanding of the substrate specificity of the UDP-N-acetylglucosamine C4 epimerase WbpP. Biochem J 2005; 389: 173-180.

234.

Feng L. , Tao J. , Guo H. et al. Structure of the Shigella dysenteriae 7 O antigen gene cluster and identification of its antigen specific genes. Microb Pathog 2004; 36: 109-115.

235.

Vinogradov EV , Shashkov AS , Knirel YA et al. Structure of the O-antigen of Francisella tularensis strain 15. Carbohydr Res 1991; 214: 289-297.

236.

Prior JL , Prior RG , Hitchen PG et al. Characterization of the O antigen gene cluster and structural analysis of the O antigen of Francisella tularensis subsp tularensis. J Med Microbiol 2003; 52: 845-851.

237.

Parolis H. , Parolis LA , Olivieri G. Structural studies on the Shigella-like Escherichia coli O121 O-specific polysaccharide. Carbohydr Res 1997; 303: 319-325.

238.

Larsen TM , Boehlein SK , Schuster SM et al. Three-dimensional structure of Escherichia coli asparagine synthetase B: a short journey from substrate to product. Biochemistry 1999; 38: 16146-16157.

239.

Kaya S. , Araki Y. , Ito E. The structure of the O-specific chain of lipopolysaccharide from Pseudomonas aeruginosa IID 1012 (ATCC 27588). J Biochem 1989; 105: 29-34.

240.

Schuman B. , Alfaro JA , Evans SV Glycosyltransferase structure and function. In: Peters T. (ed). Bioactive Conformation I. Berlin: Springer, 2007 ; 217-257.

241.

Knirel YA , Kochetkov NK [Structure of lipopolysaccharides from Gram-negative bacteria. III. Structure of O-specific polysaccharides]. Biokhimiia 1994; 59: 1784-1851.

242.

Moreau M. , Richards JC , Fournier JM , Byrd RA , Karakawa WW , Vann WF Structure of the type 5 capsular polysaccharide of Staphylococcus aureus. Carbohydr Res 1990; 201: 285-297.

243.

Fournier JM , Vann WF , Karakawa WW Purification and characterization of Staphylococcus aureus type 8 capsular polysaccharide. Infect Immun 1984; 45: 87-93.

244.

Jones C. , Currie F. , Forster MJ N.M.R. and conformational analysis of the capsular polysaccharide from Streptococcus pneumoniae type 4. Carbohydr Res 1991; 221: 95-121.

245.

Schmidt MA , Jann B. , Jann K. Cell-wall lipopolysaccharide of the urinary-tract-infective Escherichia coli O4:K12:H-. Structure of the polysaccharide chain. Eur J Biochem 1983 ; 137: 163-171.

246.

Manca MC , Weintraub A. , Widmalm G. Structural studies of the Escherichia coli O26 O-antigen polysaccharide . Carbohydr Res 1996; 281: 155-160.

247.

Landersjö C. , Weintraub A. , Widmalm G. Structural analysis of the O-antigen polysaccharide from the Shiga toxin-producing Escherichia coli O172. Eur J Biochem 2001; 268: 2239-2245.

248.

Kneidinger B. , O’Riordan K. , Li J. , Brisson JR , Lee JC , Lam JS Three highly conserved proteins catalyze the conversion of UDP-N-acetyl-D-glucosamine to precursors for the biosynthesis of O antigen in Pseudomonas aeruginosa O11 and capsule in Staphylococcus aureus type 5. Implications for the UDP-Nacetyl-L-fucosamine biosynthetic pathway. J Biol Chem 2003; 278: 3615-3627.

249.

Mulrooney EF , Poon KK , McNally DJ , Brisson JR , Lam JS Biosynthesis of UDP-N-acetyl-L-fucosamine, a precursor to the biosynthesis of lipopolysaccharide in Pseudomonas aeruginosa serotype O11. J Biol Chem 2005; 280: 19535-19542.

250.

Guerry P. , Doig P. , Alm RA , Burr DH , Kinsella N. , Trust TJ Identification and characterization of genes required for post-translational modification of Campylobacter coli VC167 flagellin. Mol Microbiol 1996; 19: 369-378.

251.

Glaze PA , Watson DC , Young NM , Tanner ME Biosynthesis of CMP-N,N’-diacetyllegionaminic acid from UDP-N,N’-diacetyl-bacillosamine in Legionella pneumophila. Biochemistry 2008 ; 47: 3272-3282.

252.

Vann WF , Daines DA , Murkin AS et al. The NeuC protein of Escherichia coli K1 is a UDP N-acetylglucosamine 2-epimerase. J Bacteriol 2004; 186: 706-712.

253.

Marchler-Bauer A. , Anderson JB , Derbyshire MK et al. CDD: a conserved domain database for interactive domain family analysis. Nucleic Acids Res 2007; 35: D237-D240.

254.

Franklin MJ , Chitnis CE , Gacesa P. , Sonesson A. , White DC , Ohman DE Pseudomonas aeruginosa AlgG is a polymer level alginate C5-mannuronan epimerase. J Bacteriol 1994; 176: 1821-1830.

255.

King JD , Harmer NJ , Preston A. et al. Predicting protein function from structure - the roles of short-chain dehydrogenase/reductase enzymes in Bordetella O-antigen biosynthesis. J Mol Biol 2007; 374: 749-763.

256.

Faure K. , Shimabukuro D. , Ajayi T. , Allmond LR , Sawa T. , Wiener-Kronish JP O-antigen serotypes and type III secretory toxins in clinical isolates of Pseudomonas aeruginosa. J Clin Microbiol 2003 ; 41: 2158-2160.

257.

Persson B. , Kallberg Y. , Oppermann U. , Jornvall H. Coenzyme-based functional assignments of short-chain dehydrogenases/ reductases (SDRs). Chem Biol Interact 2003; 143/144: 271-278.

258.

Libisch B. , Balogh B. , Fuzi M. Identification of two multidrug-resistant Pseudomonas aeruginosa clonal lineages with a countrywide distribution in Hungary. Curr Microbiol 2009 ; 58: 111-116.

259.

Kaluzny K. , Abeyrathne PD , Lam JS Coexistence of two distinct versions of O-antigen polymerase, Wzy-alpha and Wzy-beta, in Pseudomonas aeruginosa serogroup O2 and their contributions to cell surface diversity . J Bacteriol 2007; 189: 4141-4152.

260.

Liu D. , Cole RA , Reeves PR An O-antigen processing function for Wzx (RfbX): a promising candidate for O-unit flippase. J Bacteriol 1996; 178: 2102-2107.

261.

Burrows LL , Lam JS Effect of wzx (rfbX) mutations on A-band and B-band lipopolysaccharide biosynthesis in Pseudomonas aeruginosa O5. J Bacteriol 1999; 181: 973-980.

262.

Marolda CL , Vicarioli J. , Valvano MA Wzx proteins involved in biosynthesis of O antigen function in association with the first sugar of the O-specific lipopolysaccharide subunit. Microbiology 2004; 150: 4095-4105.

263.

Feldman MF , Marolda CL , Monteiro MA , Perry MB , Parodi AJ , Valvano MA The activity of a putative polyisoprenol-linked sugar translocase (Wzx) involved in Escherichia coli O antigen assembly is independent of the chemical structure of the O repeat. J Biol Chem 1999; 274: 35129-35138.

264.

Daniels C. , Vindurampulle C. , Morona R. Overexpression and topology of the Shigella flexneri O-antigen polymerase (Rfc/ Wzy). Mol Microbiol 1998; 28: 1211-1222.

265.

Jiang SM , Wang L. , Reeves PR Molecular characterization of Streptococcus pneumoniae type 4, 6B, 8, and 18C capsular polysaccharide gene clusters. Infect Immun 2001; 69: 1244-1255.

266.

Newton GJ , Daniels C. , Burrows LL , Kropinski AM , Clarke AJ , Lam JS Three-component-mediated serotype conversion in Pseudomonas aeruginosa by bacteriophage D3. Mol Microbiol 2001; 39: 1237-1247.

267.

Burrows LL , Chow D. , Lam JS Pseudomonas aeruginosa B-band O-antigen chain length is modulated by Wzz (Rol). J Bacteriol 1997; 179: 1482-1489.

268.

Daniels C. , Griffiths C. , Cowles B. , Lam JS Pseudomonas aeruginosa O-antigen chain length is determined before ligation to lipid A core. Environ Microbiol 2002; 4: 883-897.

269.

Kintz E. , Scarff JM , DiGiandomenico A. , Goldberg JB Lipopolysaccharide O-antigen chain length regulation in Pseudomonas aeruginosa serogroup O11 strain PA103. J Bacteriol 2008 ; 190: 2709-2716.

270.

Abeyrathne PD , Lam JS WaaL of Pseudomonas aeruginosa utilizes ATP in in vitro ligation of O antigen onto lipid A-core. Mol Microbiol 2007; 65: 1345-1359.

271.

Pérez JM , McGarry MA , Marolda CL , Valvano MA Functional analysis of the large periplasmic loop of the Escherichia coli K-12 WaaL O-antigen ligase. Mol Microbiol 2008; 70: 1424-1440.

272.

Heinrichs DE , Monteiro MA , Perry MB , Whitfield C. The assembly system for the lipopolysaccharide R2 core-type of Escherichia coli is a hybrid of those found in Escherichia coli K-12 and Salmonella enterica. Structure and function of the R2 WaaK and WaaL homologs. J Biol Chem 1998; 273: 8849-8859.