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pp 1-34 | Cite as

Bacterial Glycoengineering as a Biosynthetic Route to Customized Glycomolecules

  • Laura E. Yates
  • Dominic C. Mills
  • Matthew P. DeLisa
Chapter
Part of the Advances in Biochemical Engineering/Biotechnology book series

Abstract

Bacteria have garnered increased interest in recent years as a platform for the biosynthesis of a variety of glycomolecules such as soluble oligosaccharides, surface-exposed carbohydrates, and glycoproteins. The ability to engineer commonly used laboratory species such as Escherichia coli to efficiently synthesize non-native sugar structures by recombinant expression of enzymes from various carbohydrate biosynthesis pathways has allowed for the facile generation of important products such as conjugate vaccines, glycosylated outer membrane vesicles, and a variety of other research reagents for studying and understanding the role of glycans in living systems. This chapter highlights some of the key discoveries and technologies for equipping bacteria with the requisite biosynthetic machinery to generate such products. As the bacterial glyco-toolbox continues to grow, these technologies are expected to expand the range of glycomolecules produced recombinantly in bacterial systems, thereby opening up this platform to an even larger number of applications.

Graphical Abstract

Keywords

Bacterial oligosaccharyltransferase Bacterial polysaccharides Bacterial protein glycosylation Carbohydrate biosynthesis pathways Conjugate vaccines Glycoengineering Glycosyltransferase 

Abbreviations

ABC-transporter

ATP-binding cassette transporter

CPS

Capsular polysaccharide

diNAcBac

Bacillosamine

ECA

Enterobacterial common antigen

EPA

Exotoxin A from Pseudomonas aeruginosa

EPO

Erythropoietin

Gal

Galactose

GalNAc

N-Acetylgalactosamine

Gb3

Globotriaosylceramide

Gb4

Globotetraosylceramide

Glc

Glucose

GlcNAc

N-Acetylglucosamine

GM

Monosialotetrahexosylganglioside

HA

Hyaluronic acid

hGH

Human growth hormone

Hib

Haemophilus influenza type b

IgG

Immunoglobulin G

LacNAc

N-Acetyllactosamine

LeX

Lewis X antigen

Ley

Lewis Y antigen

LOS

Lipo-oligosaccharide

LPS

Lipopolysaccharide

Man

Mannose

MBP

Maltose binding protein

NCAM

Neural cell adhesion molecule

NeuNAc

N-Acetylneuraminic acid

OMV

Outer membrane vesicle

PEG

Polyethylene glycol

PolySia

Polysialic acid

S-layer

Surface layer

STEC

Shigatoxin producing Escherichia coli

STX

Shiga toxin

T-antigen

Thomsen–Friedenreich antigen

Und-PP

Undecaprenyl pyrophosphate

References

  1. 1.
    Herget S, Toukach PV, Ranzinger R, Hull WE, Knirel YA, von der Lieth CW (2008) Statistical analysis of the Bacterial Carbohydrate Structure Data Base (BCSDB): characteristics and diversity of bacterial carbohydrates in comparison with mammalian glycans. BMC Struct Biol 8:35Google Scholar
  2. 2.
    Senchenkova SN, Guo X, Naumenko OI, Shashkov AS, Perepelov AV, Liu B, Knirel YA (2016) Structure and genetics of the O-antigens of Escherichia coli O182-O187. Carbohydr Res 435:58–67Google Scholar
  3. 3.
    Stenutz R, Weintraub A, Widmalm G (2006) The structures of Escherichia coli O-polysaccharide antigens. FEMS Microbiol Rev 30(3):382–403Google Scholar
  4. 4.
    Whitfield C (2006) Biosynthesis and assembly of capsular polysaccharides in Escherichia coli. Annu Rev Biochem 75:39–68Google Scholar
  5. 5.
    Kuhn HM, Meier-Dieter U, Mayer H (1988) ECA, the enterobacterial common antigen. FEMS Microbiol Rev 4(3):195–222Google Scholar
  6. 6.
    Aoki-Kinoshita KF, Kanehisa M (2015) Glycomic analysis using KEGG GLYCAN. Methods Mol Biol 1273:97–107Google Scholar
  7. 7.
    Ruffing A, Chen RR (2006) Metabolic engineering of microbes for oligosaccharide and polysaccharide synthesis. Microb Cell Factories 5:25Google Scholar
  8. 8.
    Sleytr UB (1975) Heterologous reattachment of regular arrays of glycoproteins on bacterial surfaces. Nature 257(5525):400–402Google Scholar
  9. 9.
    Sleytr UB, Thorne KJ (1976) Chemical characterization of the regularly arranged surface layers of Clostridium thermosaccharolyticum and Clostridium thermohydrosulfuricum. J Bacteriol 126(1):377–383Google Scholar
  10. 10.
    Castric P (1995) pilO, a gene required for glycosylation of Pseudomonas aeruginosa 1244 pilin. Microbiology 141(5):1247–1254Google Scholar
  11. 11.
    Grass S, Buscher AZ, Swords WE, Apicella MA, Barenkamp SJ, Ozchlewski N, St Geme 3rd JW (2003) The Haemophilus influenzae HMW1 adhesin is glycosylated in a process that requires HMW1C and phosphoglucomutase, an enzyme involved in lipooligosaccharide biosynthesis. Mol Microbiol 48(3):737–751Google Scholar
  12. 12.
    Szymanski CM, Yao R, Ewing CP, Trust TJ, Guerry P (1999) Evidence for a system of general protein glycosylation in Campylobacter jejuni. Mol Microbiol 32(5):1022–1030Google Scholar
  13. 13.
    Thibault P, Logan SM, Kelly JF, Brisson JR, Ewing CP, Trust TJ, Guerry P (2001) Identification of the carbohydrate moieties and glycosylation motifs in Campylobacter jejuni flagellin. J Biol Chem 276(37):34862–34870Google Scholar
  14. 14.
    Wacker M, Linton D, Hitchen PG, Nita-Lazar M, Haslam SM, North SJ, Panico M, Morris HR, Dell A, Wren BW, Aebi M (2002) N-Linked glycosylation in Campylobacter jejuni and its functional transfer into E. coli. Science 298(5599):1790–1793Google Scholar
  15. 15.
    Feldman MF, Wacker M, Hernandez M, Hitchen PG, Marolda CL, Kowarik M, Morris HR, Dell A, Valvano MA, Aebi M (2005) Engineering N-linked protein glycosylation with diverse O antigen lipopolysaccharide structures in Escherichia coli. Proc Natl Acad Sci U S A 102(8):3016–3021Google Scholar
  16. 16.
    Kowarik M, Young NM, Numao S, Schulz BL, Hug I, Callewaert N, Mills DC, Watson DC, Hernandez M, Kelly JF, Wacker M, Aebi M (2006) Definition of the bacterial N-glycosylation site consensus sequence. EMBO J 25(9):1957–1966Google Scholar
  17. 17.
    Wacker M, Feldman MF, Callewaert N, Kowarik M, Clarke BR, Pohl NL, Hernandez M, Vines ED, Valvano MA, Whitfield C, Aebi M (2006) Substrate specificity of bacterial oligosaccharyltransferase suggests a common transfer mechanism for the bacterial and eukaryotic systems. Proc Natl Acad Sci U S A 103(18):7088–7093Google Scholar
  18. 18.
    Kalynych S, Morona R, Cygler M (2014) Progress in understanding the assembly process of bacterial O-antigen. FEMS Microbiol Rev 38(5):1048–1065Google Scholar
  19. 19.
    Raetz CR, Whitfield C (2002) Lipopolysaccharide endotoxins. Annu Rev Biochem 71:635–700Google Scholar
  20. 20.
    Cuthbertson L, Kos V, Whitfield C (2010) ABC transporters involved in export of cell surface glycoconjugates. Microbiol Mol Biol Rev 74(3):341–362Google Scholar
  21. 21.
    Whitney JC, Howell PL (2013) Synthase-dependent exopolysaccharide secretion in Gram-negative bacteria. Trends Microbiol 21(2):63–72Google Scholar
  22. 22.
    Priem B, Gilbert M, Wakarchuk WW, Heyraud A, Samain E (2002) A new fermentation process allows large-scale production of human milk oligosaccharides by metabolically engineered bacteria. Glycobiology 12(4):235–240Google Scholar
  23. 23.
    Samain E, Drouillard S, Heyraud A, Driguez H, Geremia RA (1997) Gram-scale synthesis of recombinant chitooligosaccharides in Escherichia coli. Carbohydr Res 302(1–2):35–42Google Scholar
  24. 24.
    Drouillard S, Mine T, Kajiwara H, Yamamoto T, Samain E (2010) Efficient synthesis of 6′-sialyllactose, 6,6′-disialyllactose, and 6′-KDO-lactose by metabolically engineered E. coli expressing a multifunctional sialyltransferase from the Photobacterium sp. JT-ISH-224. Carbohydr Res 345(10):1394–1399Google Scholar
  25. 25.
    Schmid J, Sieber V, Rehm B (2015) Bacterial exopolysaccharides: biosynthesis pathways and engineering strategies. Front Microbiol 6:496Google Scholar
  26. 26.
    Liu L, Liu Y, Li J, Du G, Chen J (2011) Microbial production of hyaluronic acid: current state, challenges, and perspectives. Microb Cell Factories 10:99Google Scholar
  27. 27.
    Thonard JC, Migliore SA, Blustein R (1964) Isolation of hyaluronic acid from broth cultures of streptococci. J Biol Chem 239:726–728Google Scholar
  28. 28.
    Widner B, Behr R, Von Dollen S, Tang M, Heu T, Sloma A, Sternberg D, Deangelis PL, Weigel PH, Brown S (2005) Hyaluronic acid production in Bacillus subtilis. Appl Environ Microbiol 71(7):3747–3752Google Scholar
  29. 29.
    Yu H, Stephanopoulos G (2008) Metabolic engineering of Escherichia coli for biosynthesis of hyaluronic acid. Metab Eng 10(1):24–32Google Scholar
  30. 30.
    Jia Y, Zhu J, Chen X, Tang D, Su D, Yao W, Gao X (2013) Metabolic engineering of Bacillus subtilis for the efficient biosynthesis of uniform hyaluronic acid with controlled molecular weights. Bioresour Technol 132:427–431Google Scholar
  31. 31.
    Seviour RJ, McNeil B, Fazenda ML, Harvey LM (2011) Operating bioreactors for microbial exopolysaccharide production. Crit Rev Biotechnol 31(2):170–185Google Scholar
  32. 32.
    Klemm D, Heublein B, Fink HP, Bohn A (2005) Cellulose: fascinating biopolymer and sustainable raw material. Angew Chem Int Ed Engl 44(22):3358–3393Google Scholar
  33. 33.
    Yadav V, Paniliatis BJ, Shi H, Lee K, Cebe P, Kaplan DL (2010) Novel in vivo-degradable cellulose-chitin copolymer from metabolically engineered Gluconacetobacter xylinus. Appl Environ Microbiol 76(18):6257–6265Google Scholar
  34. 34.
    Goldberg JB, Hatano K, Meluleni GS, Pier GB (1992) Cloning and surface expression of Pseudomonas aeruginosa O antigen in Escherichia coli. Proc Natl Acad Sci U S A 89(22):10716–10720Google Scholar
  35. 35.
    Gilbert C, Robinson K, Le Page RW, Wells JM (2000) Heterologous expression of an immunogenic pneumococcal type 3 capsular polysaccharide in Lactococcus lactis. Infect Immun 68(6):3251–3260Google Scholar
  36. 36.
    Garcia-Quintanilla F, Iwashkiw JA, Price NL, Stratilo C, Feldman MF (2014) Production of a recombinant vaccine candidate against Burkholderia pseudomallei exploiting the bacterial N-glycosylation machinery. Front Microbiol 5:381Google Scholar
  37. 37.
    Cuccui J, Thomas RM, Moule MG, D’Elia RV, Laws TR, Mills DC, Williamson D, Atkins TP, Prior JL, Wren BW (2013) Exploitation of bacterial N-linked glycosylation to develop a novel recombinant glycoconjugate vaccine against Francisella tularensis. Open Biol 3(5):130002Google Scholar
  38. 38.
    Kay EJ, Yates LE, Terra VS, Cuccui J, Wren BW (2016) Recombinant expression of Streptococcus pneumoniae capsular polysaccharides in Escherichia coli. Open Biol 6(4):150243Google Scholar
  39. 39.
    Price NL, Goyette-Desjardins G, Nothaft H, Valguarnera E, Szymanski CM, Segura M, Feldman MF (2016) Glycoengineered outer membrane vesicles: a novel platform for bacterial vaccines. Sci Rep 6:24931Google Scholar
  40. 40.
    Wacker M, Wang L, Kowarik M, Dowd M, Lipowsky G, Faridmoayer A, Shields K, Park S, Alaimo C, Kelley KA, Braun M, Quebatte J, Gambillara V, Carranza P, Steffen M, Lee JC (2014) Prevention of Staphylococcus aureus infections by glycoprotein vaccines synthesized in Escherichia coli. J Infect Dis 209(10):1551–1561Google Scholar
  41. 41.
    Wetter M, Kowarik M, Steffen M, Carranza P, Corradin G, Wacker M (2013) Engineering, conjugation, and immunogenicity assessment of Escherichia coli O121 O antigen for its potential use as a typhoid vaccine component. Glycoconj J 30(5):511–522Google Scholar
  42. 42.
    Merritt JH, Ollis AA, Fisher AC, DeLisa MP (2013) Glycans-by-design: engineering bacteria for the biosynthesis of complex glycans and glycoconjugates. Biotechnol Bioeng 110(6):1550–1564Google Scholar
  43. 43.
    Paton AW, Morona R, Paton JC (2000) A new biological agent for treatment of Shiga toxigenic Escherichia coli infections and dysentery in humans. Nat Med 6(3):265–270Google Scholar
  44. 44.
    Cress BF, Englaender JA, He W, Kasper D, Linhardt RJ, Koffas MA (2014) Masquerading microbial pathogens: capsular polysaccharides mimic host-tissue molecules. FEMS Microbiol Rev 38(4):660–697Google Scholar
  45. 45.
    Focareta A, Paton JC, Morona R, Cook J, Paton AW (2006) A recombinant probiotic for treatment and prevention of cholera. Gastroenterology 130(6):1688–1695Google Scholar
  46. 46.
    Hostetter SJ, Helgerson AF, Paton JC, Paton AW, Cornick NA (2014) Therapeutic use of a receptor mimic probiotic reduces intestinal Shiga toxin levels in a piglet model of hemolytic uremic syndrome. BMC Res Notes 7:331Google Scholar
  47. 47.
    Ilg K, Yavuz E, Maffioli C, Priem B, Aebi M (2010) Glycomimicry: display of the GM3 sugar epitope on Escherichia coli and Salmonella enterica sv Typhimurium. Glycobiology 20(10):1289–1297Google Scholar
  48. 48.
    Yavuz E, Maffioli C, Ilg K, Aebi M, Priem B (2011) Glycomimicry: display of fucosylation on the lipo-oligosaccharide of recombinant Escherichia coli K12. Glycoconj J 28(1):39–47Google Scholar
  49. 49.
    Mally M, Fontana C, Leibundgut-Landmann S, Laacisse L, Fan YY, Widmalm G, Aebi M (2013) Glycoengineering of host mimicking type-2 LacNAc polymers and Lewis X antigens on bacterial cell surfaces. Mol Microbiol 87(1):112–131Google Scholar
  50. 50.
    Moe GR, Bhandari TS, Flitter BA (2009) Vaccines containing de-N-acetyl sialic acid elicit antibodies protective against neisseria meningitidis groups B and C. J Immunol 182(10):6610–6617Google Scholar
  51. 51.
    Komminoth P, Roth J, Lackie PM, Bitter-Suermann D, Heitz PU (1991) Polysialic acid of the neural cell adhesion molecule distinguishes small cell lung carcinoma from carcinoids. Am J Pathol 139(2):297–304Google Scholar
  52. 52.
    Livingston BD, Jacobs JL, Glick MC, Troy FA (1988) Extended polysialic acid chains (n greater than 55) in glycoproteins from human neuroblastoma cells. J Biol Chem 263(19):9443–9448Google Scholar
  53. 53.
    Valentine JL, Chen L, Perregaux EC, Weyant KB, Rosenthal JA, Heiss C, Azadi P, Fisher AC, Putnam D, Moe GR, Merritt JH, DeLisa MP (2016) Immunization with outer membrane vesicles displaying designer glycotopes yields class-switched, glycan-specific antibodies. Cell Chem Biol 23(6):655–665Google Scholar
  54. 54.
    Hug I, Zheng B, Reiz B, Whittal RM, Fentabil MA, Klassen JS, Feldman MF (2011) Exploiting bacterial glycosylation machineries for the synthesis of a Lewis antigen-containing glycoprotein. J Biol Chem 286(43):37887–37894Google Scholar
  55. 55.
    Atochina O, Daly-Engel T, Piskorska D, McGuire E, Harn DA (2001) A schistosome-expressed immunomodulatory glycoconjugate expands peritoneal Gr1(+) macrophages that suppress naive CD4(+) T cell proliferation via an IFN-gamma and nitric oxide-dependent mechanism. J Immunol 167(8):4293–4302Google Scholar
  56. 56.
    Srivastava L, Tundup S, Choi BS, Norberg T, Harn D (2014) Immunomodulatory glycan lacto-N-fucopentaose III requires clathrin-mediated endocytosis to induce alternative activation of antigen-presenting cells. Infect Immun 82(5):1891–1903Google Scholar
  57. 57.
    van Die I, van Vliet SJ, Nyame AK, Cummings RD, Bank CM, Appelmelk B, Geijtenbeek TB, van Kooyk Y (2003) The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x. Glycobiology 13(6):471–478Google Scholar
  58. 58.
    Atochina O, Harn D (2006) Prevention of psoriasis-like lesions development in fsn/fsn mice by helminth glycans. Exp Dermatol 15(6):461–468Google Scholar
  59. 59.
    Heimburg-Molinaro J, Lum M, Vijay G, Jain M, Almogren A, Rittenhouse-Olson K (2011) Cancer vaccines and carbohydrate epitopes. Vaccine 29(48):8802–8826Google Scholar
  60. 60.
    Valderrama-Rincon JD, Fisher AC, Merritt JH, Fan YY, Reading CA, Chhiba K, Heiss C, Azadi P, Aebi M, DeLisa MP (2012) An engineered eukaryotic protein glycosylation pathway in Escherichia coli. Nat Chem Biol 8(5):434–436Google Scholar
  61. 61.
    Van Patten SM, Hughes H, Huff MR, Piepenhagen PA, Waire J, Qiu H, Ganesa C, Reczek D, Ward PV, Kutzko JP, Edmunds T (2007) Effect of mannose chain length on targeting of glucocerebrosidase for enzyme replacement therapy of Gaucher disease. Glycobiology 17(5):467–478Google Scholar
  62. 62.
    Vella M, Pace D (2015) Glycoconjugate vaccines: an update. Expert Opin Biol Ther 15(4):529–546Google Scholar
  63. 63.
    Grijalva CG, Nuorti JP, Arbogast PG, Martin SW, Edwards KM, Griffin MR (2007) Decline in pneumonia admissions after routine childhood immunisation with pneumococcal conjugate vaccine in the USA: a time-series analysis. Lancet 369(9568):1179–1186Google Scholar
  64. 64.
    Ladhani SN (2012) Two decades of experience with the Haemophilus influenzae serotype b conjugate vaccine in the United Kingdom. Clin Ther 34(2):385–399Google Scholar
  65. 65.
    Lees A, Puvanesarajah V, Frasch CE (2008) Conjugation chemistry. In: Siber GR, Klugman KP, Makela PH (eds) Pneumococcal vaccines: the impact of conjugate vaccines. ASM Press, Washington DCGoogle Scholar
  66. 66.
    Sethuraman N, Stadheim TA (2006) Challenges in therapeutic glycoprotein production. Curr Opin Biotechnol 17(4):341–346Google Scholar
  67. 67.
    Ferrer-Miralles N, Domingo-Espin J, Corchero JL, Vazquez E, Villaverde A (2009) Microbial factories for recombinant pharmaceuticals. Microb Cell Factories 8:17Google Scholar
  68. 68.
    Bailon P, Won CY (2009) PEG-modified biopharmaceuticals. Expert Opin Drug Deliv 6(1):1–16Google Scholar
  69. 69.
    Linton D, Dorrell N, Hitchen PG, Amber S, Karlyshev AV, Morris HR, Dell A, Valvano MA, Aebi M, Wren BW (2005) Functional analysis of the Campylobacter jejuni N-linked protein glycosylation pathway. Mol Microbiol 55(6):1695–1703Google Scholar
  70. 70.
    Hug I, Feldman MF (2011) Analogies and homologies in lipopolysaccharide and glycoprotein biosynthesis in bacteria. Glycobiology 21(2):138–151Google Scholar
  71. 71.
    Young NM, Brisson JR, Kelly J, Watson DC, Tessier L, Lanthier PH, Jarrell HC, Cadotte N, St Michael F, Aberg E, Szymanski CM (2002) Structure of the N-linked glycan present on multiple glycoproteins in the Gram-negative bacterium, Campylobacter jejuni. J Biol Chem 277(45):42530–42539Google Scholar
  72. 72.
    Fisher AC, Haitjema CH, Guarino C, Celik E, Endicott CE, Reading CA, Merritt JH, Ptak AC, Zhang S, DeLisa MP (2011) Production of secretory and extracellular N-linked glycoproteins in Escherichia coli. Appl Environ Microbiol 77(3):871–881Google Scholar
  73. 73.
    Ihssen J, Kowarik M, Dilettoso S, Tanner C, Wacker M, Thony-Meyer L (2010) Production of glycoprotein vaccines in Escherichia coli. Microb Cell Factories 9:61Google Scholar
  74. 74.
    Hatz CF, Bally B, Rohrer S, Steffen R, Kramme S, Siegrist CA, Wacker M, Alaimo C, Fonck VG (2015) Safety and immunogenicity of a candidate bioconjugate vaccine against Shigella dysenteriae type 1 administered to healthy adults: a single blind, partially randomized Phase I study. Vaccine 33(36):4594–4601Google Scholar
  75. 75.
    Ravenscroft N, Haeuptle MA, Kowarik M, Fernandez FS, Carranza P, Brunner A, Steffen M, Wetter M, Keller S, Ruch C, Wacker M (2016) Purification and characterization of a Shigella conjugate vaccine, produced by glycoengineering Escherichia coli. Glycobiology 26(1):51–62Google Scholar
  76. 76.
    Kampf MM, Braun M, Sirena D, Ihssen J, Thony-Meyer L, Ren Q (2015) In vivo production of a novel glycoconjugate vaccine against Shigella flexneri 2a in recombinant Escherichia coli: identification of stimulating factors for in vivo glycosylation. Microb Cell Factories 14:12Google Scholar
  77. 77.
    Riddle MS, Kaminski RW, Di Paolo C, Porter CK, Gutierrez RL, Clarkson KA, Weerts HE, Duplessis C, Castellano A, Alaimo C, Paolino K, Gormley R, Gambillara Fonck V (2016) Safety and immunogenicity of a candidate bioconjugate vaccine against Shigella flexneri 2a administered to healthy adults: a single blind, randomized phase I study. Clin Vaccine Immunol 23(12):908–917Google Scholar
  78. 78.
    Iwashkiw JA, Fentabil MA, Faridmoayer A, Mills DC, Peppler M, Czibener C, Ciocchini AE, Comerci DJ, Ugalde JE, Feldman MF (2012) Exploiting the Campylobacter jejuni protein glycosylation system for glycoengineering vaccines and diagnostic tools directed against brucellosis. Microb Cell Factories 11:13Google Scholar
  79. 79.
    van den Dobbelsteen GP, Fae KC, Serroyen J, van den Nieuwenhof IM, Braun M, Haeuptle MA, Sirena D, Schneider J, Alaimo C, Lipowsky G, Gambillara-Fonck V, Wacker M, Poolman JT (2016) Immunogenicity and safety of a tetravalent E. coli O-antigen bioconjugate vaccine in animal models. Vaccine 34(35):4152–4160Google Scholar
  80. 80.
    Ma Z, Zhang H, Shang W, Zhu F, Han W, Zhao X, Han D, Wang PG, Chen M (2014) Glycoconjugate vaccine containing Escherichia coli O157:H7 O-antigen linked with maltose-binding protein elicits humoral and cellular responses. PLoS One 9(8):e105215Google Scholar
  81. 81.
    Ciocchini AE, Rey Serantes DA, Melli LJ, Iwashkiw JA, Deodato B, Wallach J, Feldman MF, Ugalde JE, Comerci DJ (2013) Development and validation of a novel diagnostic test for human brucellosis using a glyco-engineered antigen coupled to magnetic beads. PLoS Negl Trop Dis 7(2):e2048Google Scholar
  82. 82.
    Ciocchini AE, Serantes DA, Melli LJ, Guidolin LS, Iwashkiw JA, Elena S, Franco C, Nicola AM, Feldman MF, Comerci DJ, Ugalde JE (2014) A bacterial engineered glycoprotein as a novel antigen for diagnosis of bovine brucellosis. Vet Microbiol 172(3–4):455–465Google Scholar
  83. 83.
    Melli LJ, Ciocchini AE, Caillava AJ, Vozza N, Chinen I, Rivas M, Feldman MF, Ugalde JE, Comerci DJ (2015) Serogroup-specific bacterial engineered glycoproteins as novel antigenic targets for diagnosis of Shiga toxin-producing-escherichia coli-associated hemolytic-uremic syndrome. J Clin Microbiol 53(2):528–538Google Scholar
  84. 84.
    Shang W, Zhai Y, Ma Z, Yang G, Ding Y, Han D, Li J, Zhang H, Liu J, Wang PG, Liu XW, Chen M (2016) Production of human blood group B antigen epitope conjugated protein in Escherichia coli and utilization of the adsorption blood group B antibody. Microb Cell Factories 15(1):138Google Scholar
  85. 85.
    Glasscock CJ, Jaroentomeechai T, Yates LE, Wilson JD, Merritt JH, Lucks JB, DeLisa MP (2018) A flow cytometric approach to engineering Escherichia coli for improved eukaryotic protein glycosylation. Metab Eng 47:488–495 (in review)Google Scholar
  86. 86.
    Schwarz F, Huang W, Li C, Schulz BL, Lizak C, Palumbo A, Numao S, Neri D, Aebi M, Wang LX (2010) A combined method for producing homogeneous glycoproteins with eukaryotic N-glycosylation. Nat Chem Biol 6(4):264–266Google Scholar
  87. 87.
    Ielmini MV, Feldman MF (2011) Desulfovibrio desulfuricans PglB homolog possesses oligosaccharyltransferase activity with relaxed glycan specificity and distinct protein acceptor sequence requirements. Glycobiology 21(6):734–742Google Scholar
  88. 88.
    Jervis AJ, Langdon R, Hitchen P, Lawson AJ, Wood A, Fothergill JL, Morris HR, Dell A, Wren B, Linton D (2010) Characterization of N-linked protein glycosylation in Helicobacter pullorum. J Bacteriol 192(19):5228–5236Google Scholar
  89. 89.
    Mills DC, Jervis AJ, Abouelhadid S, Yates LE, Cuccui J, Linton D, Wren BW (2016) Functional analysis of N-linking oligosaccharyl transferase enzymes encoded by deep-sea vent proteobacteria. Glycobiology 26(4):398–409Google Scholar
  90. 90.
    Ollis AA, Chai Y, Natarajan A, Perregaux E, Jaroentomeechai T, Guarino C, Smith J, Zhang S, DeLisa MP (2015) Substitute sweeteners: diverse bacterial oligosaccharyltransferases with unique N-glycosylation site preferences. Sci Rep 5:15237Google Scholar
  91. 91.
    Schwarz F, Lizak C, Fan YY, Fleurkens S, Kowarik M, Aebi M (2011) Relaxed acceptor site specificity of bacterial oligosaccharyltransferase in vivo. Glycobiology 21(1):45–54Google Scholar
  92. 92.
    Lizak C, Gerber S, Numao S, Aebi M, Locher KP (2011) X-ray structure of a bacterial oligosaccharyltransferase. Nature 474(7351):350–355Google Scholar
  93. 93.
    Ollis AA, Zhang S, Fisher AC, DeLisa MP (2014) Engineered oligosaccharyltransferases with greatly relaxed acceptor-site specificity. Nat Chem Biol 10(10):816–822Google Scholar
  94. 94.
    Bentley SD, Aanensen DM, Mavroidi A, Saunders D, Rabbinowitsch E, Collins M, Donohoe K, Harris D, Murphy L, Quail MA, Samuel G, Skovsted IC, Kaltoft MS, Barrell B, Reeves PR, Parkhill J, Spratt BG (2006) Genetic analysis of the capsular biosynthetic locus from all 90 pneumococcal serotypes. PLoS Genet 2(3):e31Google Scholar
  95. 95.
    Jervis AJ, Butler JA, Lawson AJ, Langdon R, Wren BW, Linton D (2012) Characterization of the structurally diverse N-linked glycans of Campylobacter species. J Bacteriol 194(9):2355–2362Google Scholar
  96. 96.
    Nothaft H, Scott NE, Vinogradov E, Liu X, Hu R, Beadle B, Fodor C, Miller WG, Li J, Cordwell SJ, Szymanski CM (2012) Diversity in the protein N-glycosylation pathways within the Campylobacter genus. Mol Cell Proteomics 11(11):1203–1219Google Scholar
  97. 97.
    Santos-Silva T, Dias JM, Dolla A, Durand MC, Goncalves LL, Lampreia J, Moura I, Romao MJ (2007) Crystal structure of the 16 heme cytochrome from Desulfovibrio gigas: a glycosylated protein in a sulphate-reducing bacterium. J Mol Biol 370(4):659–673Google Scholar
  98. 98.
    Ihssen J, Haas J, Kowarik M, Wiesli L, Wacker M, Schwede T, Thony-Meyer L (2015) Increased efficiency of Campylobacter jejuni N-oligosaccharyltransferase PglB by structure-guided engineering. Open Biol 5(4):140227Google Scholar
  99. 99.
    McCann JR, St Geme 3rd JW (2014) The HMW1C-like glycosyltransferases--an enzyme family with a sweet tooth for simple sugars. PLoS Pathog 10(4):e1003977Google Scholar
  100. 100.
    Grass S, Lichti CF, Townsend RR, Gross J, St Geme 3rd JW (2010) The Haemophilus influenzae HMW1C protein is a glycosyltransferase that transfers hexose residues to asparagine sites in the HMW1 adhesin. PLoS Pathog 6(5):e1000919Google Scholar
  101. 101.
    Schwarz F, Fan YY, Schubert M, Aebi M (2011) Cytoplasmic N-glycosyltransferase of Actinobacillus pleuropneumoniae is an inverting enzyme and recognizes the NX(S/T) consensus sequence. J Biol Chem 286(40):35267–35274Google Scholar
  102. 102.
    Naegeli A, Neupert C, Fan YY, Lin CW, Poljak K, Papini AM, Schwarz F, Aebi M (2014) Molecular analysis of an alternative N-glycosylation machinery by functional transfer from Actinobacillus pleuropneumoniae to Escherichia coli. J Biol Chem 289(4):2170–2179Google Scholar
  103. 103.
    Lomino JV, Naegeli A, Orwenyo J, Amin MN, Aebi M, Wang LX (2013) A two-step enzymatic glycosylation of polypeptides with complex N-glycans. Bioorg Med Chem 21(8):2262–2270Google Scholar
  104. 104.
    Iwashkiw JA, Vozza NF, Kinsella RL, Feldman MF (2013) Pour some sugar on it: the expanding world of bacterial protein O-linked glycosylation. Mol Microbiol 89(1):14–28Google Scholar
  105. 105.
    Power PM, Seib KL, Jennings MP (2006) Pilin glycosylation in Neisseria meningitidis occurs by a similar pathway to wzy-dependent O-antigen biosynthesis in Escherichia coli. Biochem Biophys Res Commun 347(4):904–908Google Scholar
  106. 106.
    Whitfield C, Amor PA, Koplin R (1997) Modulation of the surface architecture of Gram-negative bacteria by the action of surface polymer:lipid A-core ligase and by determinants of polymer chain length. Mol Microbiol 23(4):629–638Google Scholar
  107. 107.
    Castric P, Cassels FJ, Carlson RW (2001) Structural characterization of the Pseudomonas aeruginosa 1244 pilin glycan. J Biol Chem 276(28):26479–26485Google Scholar
  108. 108.
    Faridmoayer A, Fentabil MA, Mills DC, Klassen JS, Feldman MF (2007) Functional characterization of bacterial oligosaccharyltransferases involved in O-linked protein glycosylation. J Bacteriol 189(22):8088–8098Google Scholar
  109. 109.
    Faridmoayer A, Fentabil MA, Haurat MF, Yi W, Woodward R, Wang PG, Feldman MF (2008) Extreme substrate promiscuity of the Neisseria oligosaccharyl transferase involved in protein O-glycosylation. J Biol Chem 283(50):34596–34604Google Scholar
  110. 110.
    Musumeci MA, Hug I, Scott NE, Ielmini MV, Foster LJ, Wang PG, Feldman MF (2013) In vitro activity of Neisseria meningitidis PglL O-oligosaccharyltransferase with diverse synthetic lipid donors and a UDP-activated sugar. J Biol Chem 288(15):10578–10587Google Scholar
  111. 111.
    Elhenawy W, Scott NE, Tondo ML, Orellano EG, Foster LJ, Feldman MF (2016) Protein O-linked glycosylation in the plant pathogen Ralstonia solanacearum. Glycobiology 26(3):301–311Google Scholar
  112. 112.
    Iwashkiw JA, Seper A, Weber BS, Scott NE, Vinogradov E, Stratilo C, Reiz B, Cordwell SJ, Whittal R, Schild S, Feldman MF (2012) Identification of a general O-linked protein glycosylation system in Acinetobacter baumannii and its role in virulence and biofilm formation. PLoS Pathog 8(6):e1002758Google Scholar
  113. 113.
    Lithgow KV, Scott NE, Iwashkiw JA, Thomson EL, Foster LJ, Feldman MF, Dennis JJ (2014) A general protein O-glycosylation system within the Burkholderia cepacia complex is involved in motility and virulence. Mol Microbiol 92(1):116–137Google Scholar
  114. 114.
    Vik A, Aas FE, Anonsen JH, Bilsborough S, Schneider A, Egge-Jacobsen W, Koomey M (2009) Broad spectrum O-linked protein glycosylation in the human pathogen Neisseria gonorrhoeae. Proc Natl Acad Sci U S A 106(11):4447–4452Google Scholar
  115. 115.
    Qutyan M, Henkel M, Horzempa J, Quinn M, Castric P (2010) Glycosylation of pilin and nonpilin protein constructs by Pseudomonas aeruginosa 1244. J Bacteriol 192(22):5972–5981Google Scholar
  116. 116.
    DiGiandomenico A, Matewish MJ, Bisaillon A, Stehle JR, Lam JS, Castric P (2002) Glycosylation of Pseudomonas aeruginosa 1244 pilin: glycan substrate specificity. Mol Microbiol 46(2):519–530Google Scholar
  117. 117.
    Pan C, Sun P, Liu B, Liang H, Peng Z, Dong Y, Wang D, Liu X, Wang B, Zeng M, Wu J, Zhu L, Wang H (2016) Biosynthesis of conjugate vaccines using an O-linked glycosylation system. MBio 7(2):e00443–e00416Google Scholar
  118. 118.
    Nothaft H, Szymanski CM (2010) Protein glycosylation in bacteria: sweeter than ever. Nat Rev Microbiol 8(11):765–778Google Scholar
  119. 119.
    Kudelka MR, Ju T, Heimburg-Molinaro J, Cummings RD (2015) Simple sugars to complex disease--mucin-type O-glycans in cancer. Adv Cancer Res 126:53–135Google Scholar
  120. 120.
    Henderson GE, Isett KD, Gerngross TU (2011) Site-specific modification of recombinant proteins: a novel platform for modifying glycoproteins expressed in E. coli. Bioconjug Chem 22(5):903–912Google Scholar
  121. 121.
    De Gregorio E, Rappuoli R (2014) From empiricism to rational design: a personal perspective of the evolution of vaccine development. Nat Rev Immunol 14(7):505–514Google Scholar
  122. 122.
    Kulp A, Kuehn MJ (2010) Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annu Rev Microbiol 64:163–184Google Scholar
  123. 123.
    Alaniz RC, Deatherage BL, Lara JC, Cookson BT (2007) Membrane vesicles are immunogenic facsimiles of Salmonella typhimurium that potently activate dendritic cells, prime B and T cell responses, and stimulate protective immunity in vivo. J Immunol 179(11):7692–7701Google Scholar
  124. 124.
    Ellis TN, Leiman SA, Kuehn MJ (2010) Naturally produced outer membrane vesicles from Pseudomonas aeruginosa elicit a potent innate immune response via combined sensing of both lipopolysaccharide and protein components. Infect Immun 78(9):3822–3831Google Scholar
  125. 125.
    Schild S, Nelson EJ, Camilli A (2008) Immunization with Vibrio cholerae outer membrane vesicles induces protective immunity in mice. Infect Immun 76(10):4554–4563Google Scholar
  126. 126.
    Chen DJ, Osterrieder N, Metzger SM, Buckles E, Doody AM, DeLisa MP, Putnam D (2010) Delivery of foreign antigens by engineered outer membrane vesicle vaccines. Proc Natl Acad Sci U S A 107(7):3099–3104Google Scholar
  127. 127.
    Sanders H, Feavers IM (2011) Adjuvant properties of meningococcal outer membrane vesicles and the use of adjuvants in Neisseria meningitidis protein vaccines. Expert Rev Vaccines 10(3):323–334Google Scholar
  128. 128.
    Gorringe AR, Pajon R (2012) Bexsero: a multicomponent vaccine for prevention of meningococcal disease. Hum Vaccin Immunother 8(2):174–183Google Scholar
  129. 129.
    Holst J, Martin D, Arnold R, Huergo CC, Oster P, O’Hallahan J, Rosenqvist E (2009) Properties and clinical performance of vaccines containing outer membrane vesicles from Neisseria meningitidis. Vaccine 27(Suppl 2):B3–B12Google Scholar
  130. 130.
    Muralinath M, Kuehn MJ, Roland KL, Curtiss 3rd R (2011) Immunization with Salmonella enterica serovar Typhimurium-derived outer membrane vesicles delivering the pneumococcal protein PspA confers protection against challenge with Streptococcus pneumoniae. Infect Immun 79(2):887–894Google Scholar
  131. 131.
    Liu D, Reeves PR (1994) Escherichia coli K12 regains its O antigen. Microbiology 140(1):49–57Google Scholar
  132. 132.
    Han W, Wu B, Li L, Zhao G, Woodward R, Pettit N, Cai L, Thon V, Wang PG (2012) Defining function of lipopolysaccharide O-antigen ligase WaaL using chemoenzymatically synthesized substrates. J Biol Chem 287(8):5357–5365Google Scholar
  133. 133.
    Chen L, Valentine JL, Huang CJ, Endicott CE, Moeller TD, Rasmussen JA, Fletcher JR, Boll JM, Rosenthal JA, Dobruchowska J, Wang Z, Heiss C, Azadi P, Putnam D, Trent MS, Jones BD, DeLisa MP (2016) Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies. Proc Natl Acad Sci U S A 113(26):E3609–E3618Google Scholar
  134. 134.
    Xu DQ, Cisar JO, Osorio M, Wai TT, Kopecko DJ (2007) Core-linked LPS expression of Shigella dysenteriae serotype 1 O-antigen in live Salmonella Typhi vaccine vector Ty21a: preclinical evidence of immunogenicity and protection. Vaccine 25(33):6167–6175Google Scholar
  135. 135.
    Wang L, Curd H, Reeves PR (1999) Immunization of mice with live oral vaccine based on a Salmonella enterica (sv Typhimurium) aroA strain expressing the Escherichia coli O111 O antigen. Microb Pathog 27(1):55–59Google Scholar
  136. 136.
    Nothaft H, Davis B, Lock YY, Perez-Munoz ME, Vinogradov E, Walter J, Coros C, Szymanski CM (2016) Engineering the Campylobacter jejuni N-glycan to create an effective chicken vaccine. Sci Rep 6:26511Google Scholar
  137. 137.
    Bentley R (1990) The shikimate pathway--a metabolic tree with many branches. Crit Rev Biochem Mol Biol 25(5):307–384Google Scholar
  138. 138.
    Ruby T, McLaughlin L, Gopinath S, Monack D (2012) Salmonella’s long-term relationship with its host. FEMS Microbiol Rev 36(3):600–615Google Scholar
  139. 139.
    Felgner S, Frahm M, Kocijancic D, Rohde M, Eckweiler D, Bielecka A, Bueno E, Cava F, Abraham WR, Curtiss 3rd R, Haussler S, Erhardt M, Weiss S (2016) aroA-Deficient Salmonella enterica Serovar Typhimurium is more than a metabolically attenuated mutant. MBio 7(5):e01220–e01216Google Scholar
  140. 140.
    National-Research-Council (2012) Transforming glycoscience: a roadmap for the future. The National Academies Press, Washington, DCGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature  2018

Authors and Affiliations

  • Laura E. Yates
    • 1
  • Dominic C. Mills
    • 1
  • Matthew P. DeLisa
    • 1
  1. 1.School of Chemical and Biomolecular Engineering, Cornell UniversityIthacaUSA

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