Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Glycointeractions in bacterial pathogenesis

Nature Reviews Microbiology volume 16, pages 440–452 (2018)Cite this article

Subjects

Abstract

Many important interactions between bacterial pathogens and their hosts are highly specific binding events that involve host or pathogen carbohydrate structures (glycans). Glycan interactions can mediate adhesion, invasion and immune evasion and can act as receptors for toxins. Several bacterial pathogens can also enzymatically alter host glycans to reveal binding targets, degrade the host cell glycans or alter the function of host glycoproteins. In recent years, high-throughput screening technologies, such as lectin, glycan and mucin microarrays, have transformed the field by identifying new bacterial–host glycointeractions, which are crucial for colonization, persistence and disease. In this Review, we discuss interactions involving both host and bacterial glycans that have a role in bacterial pathogenesis. We also highlight recent technological advances that have illuminated the glycoscience of microbial pathogenesis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Adherence by pathogenic bacteria mediated by bacterial or host lectins.
Fig. 2: Glycointeractomics of pathogen persistence.
Fig. 3: Glycointeractomics of bacterial toxins.
Fig. 4: Applications of lectin and glycan microarrays in glycointeractomics.

Similar content being viewed by others

References

  1. Ghazarian, H., Idoni, B. & Oppenheimer, S. B. A glycobiology review: carbohydrates, lectins and implications in cancer therapeutics. Acta Histochem. 113, 236–247 (2011).

    CAS  PubMed  Google Scholar 

  2. Moremen, K. W., Tiemeyer, M. & Nairn, A. V. Vertebrate protein glycosylation: diversity, synthesis and function. Nat. Rev. Mol. Cell Biol. 13, 448–462 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Semchenko, E. A. et al. Structural heterogeneity of terminal glycans in Campylobacter jejuni lipooligosaccharides. PLoS ONE 7, e40920 (2012).

    Google Scholar 

  4. Tao, S. C. et al. Lectin microarrays identify cell-specific and functionally significant cell surface glycan markers. Glycobiology 18, 761–769 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Tateno, H. et al. Glycome diagnosis of human induced pluripotent stem cells using lectin microarray. J. Biol. Chem. 286, 20345–20353 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Stowell, S. R. et al. Microbial glycan microarrays define key features of host-microbial interactions. Nat. Chem. Biol. 10, 470–476 (2014). This article describes the development and testing of the first bacteria-focused glycan array, enabling the analysis of how the adaptive and non-adaptive immune responses react to surface glycans.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Waespy, M. et al. Carbohydrate recognition specificity of trans-sialidase lectin domain from Trypanosoma congolense. PLoS Neglected Trop. Dis. 9, e0004120 (2015).

    Google Scholar 

  8. Naughton, J. A. et al. Divergent mechanisms of interaction of Helicobacter pylori and Campylobacter jejuni with mucus and mucins. Infect. Immun. 81, 2838–2850 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Carlin, A. F. et al. Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response. Blood 113, 3333–3336 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Secundino, I. et al. Host and pathogen hyaluronan signal through human siglec-9 to suppress neutrophil activation. J. Mol. Med. 94, 219–233 (2016). This article was the first report of a non-sialic acid interaction with a Siglec protein, providing a new role for bacterial glycosaminoglycan structures and identifying a novel mechanism of interactions with important immunomodulatory proteins.

    CAS  PubMed  Google Scholar 

  11. De Oliveira, D. M. P. et al. Blood group antigen recognition via the group a Streptococcal M protein mediates host colonization. mBio 8, e02237 (2017).

    Google Scholar 

  12. Ilver, D. et al. Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging. Science 279, 373–377 (1998).

    CAS  PubMed  Google Scholar 

  13. Mahdavi, J. et al. Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation. Science 297, 573–578 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Rossez, Y. et al. The lacdiNAc-specific adhesin LabA mediates adhesion of Helicobacter pylori to human gastric mucosa. J. Infect. Dis. 210, 1286–1295 (2014).

    CAS  PubMed  Google Scholar 

  15. Sokurenko, E. V. et al. Pathogenic adaptation of Escherichia coli by natural variation of the FimH adhesin. Proc. Natl Acad. Sci. USA 95, 8922–8926 (1998).

    CAS  PubMed  Google Scholar 

  16. King, S. J. Pneumococcal modification of host sugars: a major contributor to colonization of the human airway? Mol. Oral Microbiol. 25, 15–24 (2010).

    CAS  PubMed  Google Scholar 

  17. Johnston, J. W. et al. Regulation of sialic acid transport and catabolism in Haemophilus influenzae. Mol. Microbiol. 66, 26–39 (2007).

    CAS  PubMed  Google Scholar 

  18. Byres, E. et al. Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin. Nature 456, 648–652 (2008). This article identifies the glycan target of the SubAB toxin of E. coli as a non-human glycosylation that is incorporated after dietary intake.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Deng, L. et al. Host adaptation of a bacterial toxin from the human pathogen Salmonella Typhi. Cell 159, 1290–1299 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Shewell, L. K. et al. The cholesterol-dependent cytolysins pneumolysin and streptolysin O require binding to red blood cell glycans for hemolytic activity. Proc. Natl Acad. Sci. USA 111, E5312–E5320 (2014).

    CAS  PubMed  Google Scholar 

  21. Spaulding, C. N. et al. Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist. Nature 546, 528–532 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Gupta, K., Hooton, T. M. & Stamm, W. E. Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infections. Ann. Intern. Med. 135, 41–50 (2001).

    CAS  PubMed  Google Scholar 

  23. Sanchez, G. V., Master, R. N., Karlowsky, J. A. & Bordon, J. M. In Vitro antimicrobial resistance of urinary Escherichia coli isolates among US outpatients from 2000 to 2010. Antimicrob. Agents Chemother. 56, 2181–2183 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Roberts, J. A. et al. The Gal(alpha 1–4)Gal-specific tip adhesin of Escherichia coli P-fimbriae is needed for pyelonephritis to occur in the normal urinary tract. Proc. Natl Acad. Sci. USA 91, 11889–11893 (1994).

    CAS  PubMed  Google Scholar 

  25. Cusumano, C. K. et al. Treatment and prevention of urinary tract infection with orally active FimH inhibitors. Sci. Transl. Med. 3, 109ra115 (2011).

    PubMed  PubMed Central  Google Scholar 

  26. Guiton, P. S. et al. Combinatorial small-molecule therapy prevents uropathogenic Escherichia coli catheter-associated urinary tract infections in mice. Antimicrob. Agents Chemother. 56, 4738–4745 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Klein, T. et al. FimH antagonists for the oral treatment of urinary tract infections: from design and synthesis to in vitro and in vivo evaluation. J. Med. Chem. 53, 8627–8641 (2010).

    CAS  PubMed  Google Scholar 

  28. Totsika, M. et al. A FimH inhibitor prevents acute bladder infection and treats chronic cystitis caused by multidrug-resistant uropathogenic Escherichia coli ST131. J. Infect. Dis. 208, 921–928 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Hatakeyama, M. A. Sour relationship between BabA and Lewis b. Cell Host Microbe 21, 318–320 (2017).

    CAS  PubMed  Google Scholar 

  30. Dunne, C., Dolan, B. & Clyne, M. Factors that mediate colonization of the human stomach by Helicobacter pylori. World J. Gastroenterol. 20, 5610–5624 (2014).

    CAS  PubMed  Google Scholar 

  31. Magalhaes, A. et al. Helicobacter pylori chronic infection and mucosal inflammation switches the human gastric glycosylation pathways. Biochim. Biophys. Acta 1852, 1928–1939 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Bugaytsova, J. A. et al. Helicobacter pylori adapts to chronic infection and gastric disease via pH-responsive BabA-mediated adherence. Cell Host Microbe 21, 376–389 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Ogata, M., Araki, K. & Ogata, T. An electron microscopic study of Helicobacter pylori in the surface mucous gel layer. Histol Histopathol 13, 347–358 (1998).

    CAS  PubMed  Google Scholar 

  34. Fischetti, V. A. Streptococcal M protein: molecular design and biological behavior. Clin. Microbiol. Rev. 2, 285–314 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Frick, I. M., Schmidtchen, A. & Sjobring, U. Interactions between M proteins of Streptococcus pyogenes and glycosaminoglycans promote bacterial adhesion to host cells. Eur. J. Biochem. 270, 2303–2311 (2003).

    CAS  PubMed  Google Scholar 

  36. Maamary, P. G. et al. Tracing the evolutionary history of the pandemic group A streptococcal M1T1 clone. FASEB J. 26, 4675–4684 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Everest-Dass, A. V. et al. Comparative structural analysis of the glycosylation of salivary and buccal cell proteins: innate protection against infection by Candida albicans. Glycobiology 22, 1465–1479 (2012).

    CAS  PubMed  Google Scholar 

  38. van Kooyk, Y. & Geijtenbeek, T. B. DC-SIGN: escape mechanism for pathogens. Nat. Rev. Immunol. 3, 697–709 (2003).

    PubMed  Google Scholar 

  39. Xu, J. et al. Mannose-binding lectin inhibits the motility of pathogenic Salmonella by affecting the driving forces of motility and the chemotactic response. PLoS ONE 11, e0154165 (2016).

    Google Scholar 

  40. Edwards, J. L. & Apicella, M. A. The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women. Clin. Microbiol. Rev. 17, 965–981 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Harvey, H. A., Jennings, M. P., Campbell, C. A., Williams, R. & Apicella, M. A. Receptor-mediated endocytosis of Neisseria gonorrhoeae into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor. Mol. Microbiol. 42, 659–672 (2001).

    CAS  PubMed  Google Scholar 

  42. Patel, P. et al. Shared antigenicity and immunogenicity of type 4 pilins expressed by Pseudomonas aeruginosa, Moraxella bovis, Neisseria gonorrhoaea, Dichelobacter nodosus, and Vibrio cholerae. Infect. Immun. 59, 4674–4676 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Jennings, M. P. et al. Identification of a novel gene involved in pilin glycosylation in Neisseria meningitidis. Mol. Microbiol. 29, 975–984 (1998).

    CAS  PubMed  Google Scholar 

  44. Banerjee, A. et al. Implications of phase variation of a gene (pgtA) encoding a pilin galactosyl transferase in gonococcal pathogenesis. J. Exp. Med. 196, 147–162 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Hegge, F. T. et al. Unique modifications with phosphocholine and phosphoethanolamine define alternate antigenic forms of Neisseria gonorrhoeae type IV pili. Proc. Natl Acad. Sci. USA 101, 10798–10803 (2004).

    CAS  PubMed  Google Scholar 

  46. Power, P. M. et al. Genetic characterization of pilin glycosylation in Neisseria meningitidis. Microbiology 146, 967–979 (2000).

    CAS  PubMed  Google Scholar 

  47. Hartley, M. D. et al. Biochemical characterization of the O-linked glycosylation pathway in Neisseria gonorrhoeae responsible for biosynthesis of protein glycans containing N,Nʹ-diacetylbacillosamine. Biochemistry 50, 4936–4948 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Jennings, M. P., Jen, F. E., Roddam, L. F., Apicella, M. A. & Edwards, J. L. Neisseria gonorrhoeae pilin glycan contributes to CR3 activation during challenge of primary cervical epithelial cells. Cell. Microbiol. 13, 885–896 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Edwards, J. L., Brown, E. J., Ault, K. A. & Apicella, M. A. The role of complement receptor 3 (CR3) in Neisseria gonorrhoeae infection of human cervical epithelia. Cell. Microbiol. 3, 611–622 (2001).

    CAS  PubMed  Google Scholar 

  50. Wessels, M. R., Moses, A. E., Goldberg, J. B. & DiCesare, T. J. Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci. Proc. Natl Acad. Sci. USA 88, 8317–8321 (1991).

    CAS  PubMed  Google Scholar 

  51. Schommer, N. N., Muto, J., Nizet, V. & Gallo, R. L. Hyaluronan breakdown contributes to immune defense against group A Streptococcus. J. Biol. Chem. 289, 26914–26921 (2014).

    CAS  PubMed  Google Scholar 

  52. Jiang, D., Liang, J. & Noble, P. W. Hyaluronan in tissue injury and repair. Annu. Rev. Cell Dev. Biol. 23, 435–461 (2007).

    CAS  PubMed  Google Scholar 

  53. Crocker, P. R., Paulson, J. C. & Varki, A. Siglecs and their roles in the immune system. Nat. Rev. Immunol. 7, 255–266 (2007).

    CAS  PubMed  Google Scholar 

  54. Varki, A. Glycan-based interactions involving vertebrate sialic-acid-recognizing proteins. Nature 446, 1023–1029 (2007).

    CAS  PubMed  Google Scholar 

  55. Chang, Y. C. & Nizet, V. The interplay between Siglecs and sialylated pathogens. Glycobiology 24, 818–825 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Cao, H. A. & Crocker, P. R. Evolution of CD33-related siglecs: regulating host immune functions and escaping pathogen exploitation? Immunology 132, 18–26 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Lewis, A. L., Nizet, V. & Varki, A. Discovery and characterization of sialic acid O-acetylation in group B Streptococcus. Proc. Natl Acad. Sci. USA 101, 11123–11128 (2004).

    CAS  PubMed  Google Scholar 

  58. Carlin, A. F., Lewis, A. L., Varki, A. & Nizet, V. Group B streptococcal capsular sialic acids interact with siglecs (immunoglobulin-like lectins) on human leukocytes. J. Bacteriol. 189, 1231–1237 (2007).

    CAS  PubMed  Google Scholar 

  59. Serruto, D. et al. Neisseria meningitidis GNA2132, a heparin-binding protein that induces protective immunity in humans. Proc. Natl Acad. Sci. USA 107, 3770–3775 (2010).

    CAS  PubMed  Google Scholar 

  60. Stephens, D. S., Greenwood, B. & Brandtzaeg, P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet 369, 2196–2210 (2007).

    PubMed  Google Scholar 

  61. Jodar, L., Feavers, I. M., Salisbury, D. & Granoff, D. M. Development of vaccines against meningococcal disease. Lancet 359, 1499–1508 (2002).

    CAS  PubMed  Google Scholar 

  62. Uria, M. J. et al. A generic mechanism in Neisseria meningitidis for enhanced resistance against bactericidal antibodies. J. Exp. Med. 205, 1423–1434 (2008). This article describes that overproduction of a capsular polysaccharide can provide protection against host immune responses, even when the immune response is directed to the capsular polysaccharide.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Goldschneider, I., Gotschlich, E. C. & Artenstein, M. S. Human immunity to the meningococcus. I. The role of humoral antibodies. J. Exp. Med. 129, 1307–1326 (1969).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Richmond, P. et al. Meningococcal serogroup C conjugate vaccine is immunogenic in infancy and primes for memory. J. Infect. Dis. 179, 1569–1572 (1999).

    CAS  PubMed  Google Scholar 

  65. Figueroa, J. E. & Densen, P. Infectious diseases associated with complement deficiencies. Clin. Microbiol. Rev. 4, 359–395 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Jarvis, G. A. & Vedros, N. A. Sialic acid of group B Neisseria meningitidis regulates alternative complement pathway activation. Infect. Immun. 55, 174–180 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Marques, M. B., Kasper, D. L., Pangburn, M. K. & Wessels, M. R. Prevention of C3 deposition by capsular polysaccharide is a virulence mechanism of type III group B streptococci. Infect. Immun. 60, 3986–3993 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Pluschke, G., Mayden, J., Achtman, M. & Levine, R. P. Role of the capsule and the O antigen in resistance of O18:K1 Escherichia coli to complement-mediated killing. Infect. Immun. 42, 907–913 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Nothaft, H. & Szymanski, C. M. Protein glycosylation in bacteria: sweeter than ever. Nat. Rev. Microbiol. 8, 765–778 (2010).

    CAS  PubMed  Google Scholar 

  70. Parge, H. E. et al. Structure of the fibre-forming protein pilin at 2.6 A resolution. Nature 378, 32–38 (1995).

    CAS  PubMed  Google Scholar 

  71. Stimson, E. et al. Meningococcal pilin: a glycoprotein substituted with digalactosyl 2,4-diacetamido-2,4,6-trideoxyhexose. Mol. Microbiol. 17, 1201–1214 (1995).

    CAS  PubMed  Google Scholar 

  72. Szymanski, C. M., Yao, R., Ewing, C. P., Trust, T. J. & Guerry, P. Evidence for a system of general protein glycosylation in Campylobacter jejuni. Mol. Microbiol. 32, 1022–1030 (1999).

    CAS  PubMed  Google Scholar 

  73. Young, N. M. et al. Structure of the N-linked glycan present on multiple glycoproteins in the Gram-negative bacterium. Campylobacter jejuni. J. Biol. Chem. 277, 42530–42539 (2002).

    CAS  PubMed  Google Scholar 

  74. Scott, N. E. et al. Simultaneous glycan-peptide characterization using hydrophilic interaction chromatography and parallel fragmentation by CID, higher energy collisional dissociation, and electron transfer dissociation MS applied to the N-linked glycoproteome of Campylobacter jejuni. Mol. Cell Proteomics 10, M000031–MCP201 (2011).

    PubMed  Google Scholar 

  75. Szymanski, C. M., Burr, D. H. & Guerry, P. Campylobacter protein glycosylation affects host cell interactions. Infect. Immun. 70, 2242–2244 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Hendrixson, D. R. & DiRita, V. J. Identification of Campylobacter jejuni genes involved in commensal colonization of the chick gastrointestinal tract. Mol. Microbiol. 52, 471–484 (2004).

    CAS  PubMed  Google Scholar 

  77. Alemka, A., Nothaft, H., Zheng, J. & Szymanski, C. M. N-Glycosylation of Campylobacter jejuni surface proteins promotes bacterial fitness. Infect. Immun. 81, 1674–1682 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Grass, S. et al. The Haemophilus influenzae HMW1 adhesin is glycosylated in a process that requires HMW1C and phosphoglucomutase, an enzyme involved in lipooligosaccharide biosynthesis. Mol. Microbiol. 48, 737–751 (2003).

    CAS  PubMed  Google Scholar 

  79. Gross, J. et al. The Haemophilus influenzae HMW1 adhesin is a glycoprotein with an unusual N-linked carbohydrate modification. J. Biol. Chem. 283, 26010–26015 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Hanuszkiewicz, A. et al. Identification of the flagellin glycosylation system in Burkholderia cenocepacia and the contribution of glycosylated flagellin to evasion of human innate immune responses. J. Biol. Chem. 289, 19231–19244 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Juge, N., Tailford, L. & Owen, C. D. Sialidases from gut bacteria: a mini-review. Biochem. Soc. Trans. 44, 166–175 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Kim, S., Oh, D. B., Kang, H. A. & Kwon, O. Features and applications of bacterial sialidases. Appl. Microbiol. Biotechnol. 91, 1–15 (2011).

    CAS  PubMed  Google Scholar 

  83. Moran, A. P., Prendergast, M. M. & Appelmelk, B. J. Molecular mimicry of host structures by bacterial lipopolysaccharides and its contribution to disease. FEMS Immunol. Med. Microbiol. 16, 105–115 (1996).

    CAS  PubMed  Google Scholar 

  84. Manco, S. et al. Pneumococcal neuraminidases A and B both have essential roles during infection of the respiratory tract and sepsis. Infect. Immun. 74, 4014–4020 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Xu, G. et al. Three Streptococcus pneumoniae sialidases: three different products. J. Am. Chem. Soc. 133, 1718–1721 (2011).

    CAS  PubMed  Google Scholar 

  86. Morris, D. E., Cleary, D. W. & Clarke, S. C. Secondary bacterial infections associated with Influenza pandemics. Front. Microbiol. 8, 1041 (2017).

    PubMed  PubMed Central  Google Scholar 

  87. Nita-Lazar, M. et al. Desialylation of airway epithelial cells during influenza virus infection enhances pneumococcal adhesion via galectin binding. Mol. Immunol. 65, 1–16 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Wren, J. T. et al. Pneumococcal Neuraminidase A (NanA) promotes biofilm formation and synergizes with Influenza A virus in nasal colonization and middle ear infection. Infect. Immun. 85, e01044–16 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Bohlmann, L. et al. Functional and structural characterization of a heparanase. Nat. Chem. Biol. 11, 955–957 (2015).

    CAS  PubMed  Google Scholar 

  90. Gao, X. et al. NleB, a bacterial effector with glycosyltransferase activity, targets GAPDH function to inhibit NF-kappaB activation. Cell Host Microbe 13, 87–99 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Wong, A. R. et al. Enteropathogenic and enterohaemorrhagic Escherichia coli: even more subversive elements. Mol. Microbiol. 80, 1420–1438 (2011).

    CAS  PubMed  Google Scholar 

  92. Pearson, J. S. et al. A type III effector antagonizes death receptor signalling during bacterial gut infection. Nature 501, 247–251 (2013). This article identifies a novel host modification process that enables EPEC to inhibit infection-induced apoptosis of host cells.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Kulkarni, A. A., Weiss, A. A. & Iyer, S. S. Glycan-based high-affinity ligands for toxins and pathogen receptors. Med. Res. Rev. 30, 327–393 (2010). This is an excellent review on interactions between glycans and bacterial toxins.

    CAS  PubMed  Google Scholar 

  94. Sandvig, K. & van Deurs, B. Membrane traffic exploited by protein toxins. Annu. Rev. Cell Dev. Biol. 18, 1–24 (2002).

    CAS  PubMed  Google Scholar 

  95. Paton, J. C. & Paton, A. W. Pathogenesis and diagnosis of Shiga toxin-producing Escherichia coli infections. Clin. Microbiol. Rev. 11, 450–479 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Schiavo, G. & van der Goot, F. G. The bacterial toxin toolkit. Nat. Rev. Mol. Cell Biol. 2, 530–537 (2001).

    CAS  PubMed  Google Scholar 

  97. Paton, A. W., Srimanote, P., Talbot, U. M., Wang, H. & Paton, J. C. A new family of potent AB(5) cytotoxins produced by Shiga toxigenic Escherichia coli. J. Exp. Med. 200, 35–46 (2004).

    CAS  PubMed  Google Scholar 

  98. Ng, P. S. et al. Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors. Nat. Commun. 5, 5750 (2014). This article provides an excellent example of using saturation transfer difference NMR for glycointeractomics using whole virus with this technique.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Peri, S., Kulkarni, A., Feyertag, F., Berninsone, P. M. & Alvarez-Ponce, D. Phylogenetic distribution of CMP-Neu5Ac Hydroxylase (CMAH), the enzyme synthetizing the proinflammatory human Xenoantigen Neu5Gc. Genome Biol. Evol. 10, 207–219 (2018).

    CAS  PubMed  Google Scholar 

  100. Varki, A. Multiple changes in sialic acid biology during human evolution. Glycoconj J. 26, 231–245 (2009).

    CAS  PubMed  Google Scholar 

  101. Bardor, M., Nguyen, D. H., Diaz, S. & Varki, A. Mechanism of uptake and incorporation of the non-human sialic acid N-glycolylneuraminic acid into human cells. J. Biol. Chem. 280, 4228–4237 (2005).

    CAS  PubMed  Google Scholar 

  102. Tangvoranuntakul, P. et al. Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid. Proc. Natl Acad. Sci. USA 100, 12045–12050 (2003).

    CAS  PubMed  Google Scholar 

  103. Parry, C. M., Hien, T. T., Dougan, G., White, N. J. & Farrar, J. J. Typhoid fever. N. Engl. J. Med. 347, 1770–1782 (2002).

    CAS  PubMed  Google Scholar 

  104. Raffatellu, M., Wilson, R. P., Winter, S. E. & Baumler, A. J. Clinical pathogenesis of typhoid fever. J. Infect. Dev. Ctries 2, 260–266 (2008).

    PubMed  Google Scholar 

  105. Song, J., Gao, X. & Galan, J. E. Structure and function of the Salmonella Typhi chimaeric A(2)B(5) typhoid toxin. Nature 499, 350–354 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Paton, J. C., Andrew, P. W., Boulnois, G. J. & Mitchell, T. J. Molecular analysis of the pathogenicity of Streptococcus pneumoniae: the role of pneumococcal proteins. Annu. Rev. Microbiol. 47, 89–115 (1993).

    CAS  PubMed  Google Scholar 

  107. Ramachandran, R., Tweten, R. K. & Johnson, A. E. Membrane-dependent conformational changes initiate cholesterol-dependent cytolysin oligomerization and intersubunit beta-strand alignment. Nat. Struct. Mol. Biol. 11, 697–705 (2004).

    CAS  PubMed  Google Scholar 

  108. Blixt, O. et al. Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proc. Natl Acad. Sci. USA 101, 17033–17038 (2004).

    CAS  PubMed  Google Scholar 

  109. Flannery, A., Gerlach, J. Q., Joshi, L. & Kilcoyne, M. Assessing bacterial interactions using carbohydrate-based microarrays. Microarrays 4, 690–713 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Song, X., Heimburg-Molinaro, J., Smith, D. F. & Cummings, R. D. Glycan microarrays of fluorescently-tagged natural glycans. Glycoconj J. 32, 465–473 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Disney, M. D. & Seeberger, P. H. The use of carbohydrate microarrays to study carbohydrate-cell interactions and to detect pathogens. Chem. Biol. 11, 1701–1707 (2004).

    CAS  PubMed  Google Scholar 

  112. Wang, D., Liu, S., Trummer, B. J., Deng, C. & Wang, A. Carbohydrate microarrays for the recognition of cross-reactive molecular markers of microbes and host cells. Nat. Biotechnol. 20, 275–281 (2002).

    CAS  PubMed  Google Scholar 

  113. Batista, B. S., Eng, W. S., Pilobello, K. T., Hendricks-Munoz, K. D. & Mahal, L. K. Identification of a conserved glycan signature for microvesicles. J. Proteome Res. 10, 4624–4633 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Ribeiro, J. P. & Mahal, L. K. Dot by dot: analyzing the glycome using lectin microarrays. Curr. Opin. Chem. Biol. 17, 827–831 (2013).

    CAS  PubMed  Google Scholar 

  115. Ekins, R. P. Multi-analyte immunoassay. J. Pharm. Biomed. Anal. 7, 155–168 (1989).

    CAS  PubMed  Google Scholar 

  116. Day, C. J. et al. Glycan:glycan interactions: high affinity biomolecular interactions that can mediate binding of pathogenic bacteria to host cells. Proc. Natl Acad. Sci. USA 112, E7266–E7275 (2015). This article describes the identification of wide-ranging glycan–glycan interactions between four different pathogens and host sugars.

    CAS  PubMed  Google Scholar 

  117. Mubaiwa, T. D. et al. The glycointeractome of serogroup B Neisseria meningitidis strain MC58. Sci. Rep. 7, 5693 (2017). This article provides an excellent example of glycointeractomics work flow, using whole bacteria, mutants and purified surface factors to identify the glycan-interacting features of N. meningitidis.

    PubMed  PubMed Central  Google Scholar 

  118. Haselhorst, T. et al. Recognition of the GM3 ganglioside glycan by Rhesus rotavirus particles. Angew. Chem. Int. Ed Engl. 50, 1055–1058 (2011).

    CAS  PubMed  Google Scholar 

  119. Kalograiaki, I. et al. Combined bacteria microarray and quartz crystal microbalance approach for exploring glycosignatures of nontypeable Haemophilus influenzae and recognition by host lectins. Anal. Chem. 88, 5950–5957 (2016).

    CAS  PubMed  Google Scholar 

  120. Lieth, C.-W.v.d., Lütteke, T. & Frank, M. Bioinformatics for glycobiology and glycomics: an introduction (Wiley-Blackwell, 2009).

  121. Porter, A. et al. A motif-based analysis of glycan array data to determine the specificities of glycan-binding proteins. Glycobiology 20, 369–380 (2010).

    CAS  PubMed  Google Scholar 

  122. Krishnamoorthy, L. & Mahal, L. K. Glycomic analysis: an array of technologies. ACS Chem. Biol. 4, 715–732 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Hsu, K. L., Pilobello, K. T. & Mahal, L. K. Analyzing the dynamic bacterial glycome with a lectin microarray approach. Nat. Chem. Biol. 2, 153–157 (2006).

    CAS  PubMed  Google Scholar 

  124. Oyelaran, O. & Gildersleeve, J. C. Glycan arrays: recent advances and future challenges. Curr. Opin. Chem. Biol. 13, 406–413 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Heimburg-Molinaro, J., Song, X., Smith, D. F. & Cummings, R. D. Preparation and analysis of glycan microarrays. Curr. Protoc. Protein Sci. https://doi.org/10.1002/0471140864.ps1210s64 (2011).

  126. Rillahan, C. D. & Paulson, J. C. Glycan microarrays for decoding the glycome. Annu. Rev. Biochem. 80, 797–823 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Smith, D. F. & Cummings, R. D. Application of microarrays for deciphering the structure and function of the human glycome. Mol. Cell Proteomics 12, 902–912 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Feizi, T. & Chai, W. G. Oligosaccharide microarrays to decipher the glyco code. Nat. Rev. Mol. Cell Biol. 5, 582–588 (2004).

    CAS  PubMed  Google Scholar 

  129. Cummings, R. D. The repertoire of glycan determinants in the human glycome. Mol. BioSyst. 5, 1087–1104 (2009).

    CAS  PubMed  Google Scholar 

  130. Day, C. J. et al. A direct-sensing galactose chemoreceptor recently evolved in invasive strains of Campylobacter jejuni. Nat. Commun. 7, 13206 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. McGuckin, M. A., Linden, S. K., Sutton, P. & Florin, T. H. Mucin dynamics and enteric pathogens. Nat. Rev. Microbiol. 9, 265–278 (2011).

    CAS  PubMed  Google Scholar 

  132. Kilcoyne, M. et al. Construction of a natural mucin microarray and interrogation for biologically relevant glyco-epitopes. Anal. Chem. 84, 3330–3338 (2012).

    CAS  PubMed  Google Scholar 

  133. Brown, A. & Higgins, M. K. Carbohydrate binding molecules in malaria pathology. Curr. Opin. Struct. Biol. 20, 560–566 (2010).

    CAS  PubMed  Google Scholar 

  134. Zhao, H., Yang, Y., von Itzstein, M. & Zhou, Y. Carbohydrate-binding protein identification by coupling structural similarity searching with binding affinity prediction. J. Comput. Chem. 35, 2177–2183 (2014).

    CAS  PubMed  Google Scholar 

  135. Yang, Y., Zhan, J., Zhao, H. & Zhou, Y. A new size-independent score for pairwise protein structure alignment and its application to structure classification and nucleic-acid binding prediction. Proteins 80, 2080–2088 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Taherzadeh, G., Zhou, Y., Liew, A. W. & Yang, Y. Sequence-based prediction of protein-carbohydrate binding sites using support vector machines. J. Chem. Inf. Model. 56, 2115–2122 (2016).

    CAS  PubMed  Google Scholar 

  137. Spillmann, D. & Burger, M. M. Carbohydrate-carbohydrate interactions in adhesion. J. Cell. Biochem. 61, 562–568 (1996).

    CAS  PubMed  Google Scholar 

  138. Varki, A. Selectin ligands. Proc. Natl Acad. Sci. USA 91, 7390–7397 (1994).

    CAS  PubMed  Google Scholar 

  139. Moran, A. P., Gupta, A. & Joshi, L. Sweet-talk: role of host glycosylation in bacterial pathogenesis of the gastrointestinal tract. Gut 60, 1412–1425 (2011).

    CAS  PubMed  Google Scholar 

  140. Popescu, O., Checiu, I., Gherghel, P., Simon, Z. & Misevic, G. N. Quantitative and qualitative approach of glycan-glycan interactions in marine sponges. Biochimie 85, 181–188 (2003).

    CAS  PubMed  Google Scholar 

  141. Bucior, I., Scheuring, S., Engel, A. & Burger, M. M. Carbohydrate-carbohydrate interaction provides adhesion force and specificity for cellular recognition. J. Cell Biol. 165, 529–537 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Humphreys, T. Chemical dissolution and in vitro reconstruction of sponge cell adhesions: I. Isolation and functional demonstration of the components involved. Dev. Biol. 8, 27–47 (1963).

    CAS  PubMed  Google Scholar 

  143. Handa, K. et al. Le(x) glycan mediates homotypic adhesion of embryonal cells independently from E-cadherin: a preliminary note. Biochem. Biophys. Res. Commun. 358, 247–252 (2007).

    CAS  PubMed  Google Scholar 

  144. Iwabuchi, K., Yamamura, S., Prinetti, A., Handa, K. & Hakomori, S. GM3-enriched microdomain involved in cell adhesion and signal transduction through carbohydrate-carbohydrate interaction in mouse melanoma B16 cells. J. Biol. Chem. 273, 9130–9138 (1998).

    CAS  PubMed  Google Scholar 

  145. Kojima, N. & Hakomori, S. Specific interaction between gangliotriaosylceramide (Gg3) and sialosyllactosylceramide (GM3) as a basis for specific cellular recognition between lymphoma and melanoma cells. J. Biol. Chem. 264, 20159–20162 (1989).

    CAS  PubMed  Google Scholar 

  146. Sava, I. G. et al. Novel interactions of glycosaminoglycans and bacterial glycolipids mediate binding of enterococci to human cells. J. Biol. Chem. 284, 18194–18201 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Giuliani, M. M. et al. A universal vaccine for serogroup B meningococcus. Proc. Natl Acad. Sci. USA 103, 10834–10839 (2006).

    CAS  PubMed  Google Scholar 

  148. Jasti, A. K. et al. Guillain-Barre syndrome: causes, immunopathogenic mechanisms and treatment. Expert Rev. Clin. Immunol. 12, 1175–1189 (2016).

    CAS  PubMed  Google Scholar 

  149. Cunningham, M. W. in Streptococcus pyogenes: Basic Biology to Clinical Manifestations (eds Ferretti, J. J., Stevens, D. L. & Fischetti, V.A.) (University of Oklahoma Health Sciences Center Library, 2016).

  150. Machado Ribeiro, F. & Goldenberg, T. Mycobacteria and autoimmunity. Lupus 24, 374–381 (2015).

    CAS  PubMed  Google Scholar 

  151. Radic, M. Role of Helicobacter pylori infection in autoimmune systemic rheumatic diseases. World J. Gastroenterol. 20, 12839–12846 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Janssen, R. et al. Host-pathogen interactions in Campylobacter infections: the host perspective. Clin. Microbiol. Rev. 21, 505–518 (2008).

    PubMed  PubMed Central  Google Scholar 

  153. Monzavi-Karbassi, B., Cunto-Amesty, G., Luo, P. & Kieber-Emmons, T. Peptide mimotopes as surrogate antigens of carbohydrates in vaccine discovery. Trends Biotechnol. 20, 207–214 (2002).

    CAS  PubMed  Google Scholar 

  154. Kiseleva, E. P. et al. Isolation and structural identification of glycopolymers of Bifidobacterium bifidum BIM B-733D as putative players in pathogenesis of autoimmune thyroid diseases. Benef. Microbes 4, 375–391 (2013).

    CAS  PubMed  Google Scholar 

  155. Mazmanian, S. K., Round, J. L. & Kasper, D. L. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453, 620–625 (2008).

    CAS  PubMed  Google Scholar 

  156. Arike, L., Holmen-Larsson, J. & Hansson, G. C. Intestinal Muc2 mucin O-glycosylation is affected by microbiota and regulated by differential expression of glycosyltranferases. Glycobiology 27, 318–328 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Pickard, J. M., Zeng, M. Y., Caruso, R. & Nunez, G. Gut microbiota: role in pathogen colonization, immune responses, and inflammatory disease. Immunol. Rev. 279, 70–89 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Umesaki, Y., Tohyama, K. & Mutai, M. Appearance of fucolipid after conventionalization of germ-free mice. J. Biochem. 90, 559–561 (1981).

    CAS  PubMed  Google Scholar 

  159. Merry, C. L. R., Lyon, M., Deakin, J. A., Hopwood, J. J. & Gallagher, J. T. Highly sensitive sequencing of the sulfated domains of heparan sulfate. J. Biol. Chem. 274, 18455–18462 (1999).

    CAS  PubMed  Google Scholar 

  160. Wuhrer, M. Glycomics using mass spectrometry. Glycoconj. J. 30, 11–22 (2013).

    CAS  PubMed  Google Scholar 

  161. Taylor, M. E. & Drickamer, K. Introduction to glycobiology (Oxford Univ. Press, 2011).

  162. Zaia, J. Mass spectrometry and glycomics. OMICS 14, 401–418 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Hinneburg, H. et al. Distinguishing N-acetylneuraminic acid linkage isomers on glycopeptides by ion mobility-mass spectrometry. Chem. Commun. 52, 4381–4384 (2016).

    CAS  Google Scholar 

  164. Gustafsson, O. J. et al. MALDI imaging mass spectrometry of N-linked glycans on formalin-fixed paraffin-embedded murine kidney. Anal. Bioanal Chem. 407, 2127–2139 (2015).

    CAS  PubMed  Google Scholar 

  165. Le Nours, J. et al. Structural basis of subtilase cytotoxin SubAB assembly. J. Biol. Chem. 288, 27505–27516 (2013).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by a National Health and Medical Research Council (NHMRC) Program Grant 1071659 to J.C.P., M.v.I. and M.P.J., Principal Research Fellowship 1138466 to M.P.J. and Project Grant 1108124 to M.P.J. and C.J.D.

Author information

Authors and Affiliations

  1. Institute for Glycomics, Griffith University, Gold Coast Campus, Gold Coast, Australia

    Jessica Poole, Christopher J. Day, Mark von Itzstein & Michael P. Jennings

  2. Research Centre for Infectious Diseases, Department of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia

    James C. Paton

Authors
  1. Jessica Poole
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher J. Day
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark von Itzstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James C. Paton
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael P. Jennings
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

J.P., C.J.D., M.v.I., J.C.P. and M.P.J. conducted the literature review for this article. J.P., C.J.D., M.v.I., J.C.P. and M.P.J. substantially contributed to discussion of content and wrote the article. J.P., C.J.D. and M.P.J. designed the figures. J.P., C.J.D., J.C.P. and M.P.J. reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Michael P. Jennings.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related Links

RCSB Protein Databank: http://www.rcsb.org/pdb/home/home.do

Glossary

Lectin

A carbohydrate-binding protein that is not an anti-carbohydrate antibody and does not modify the carbohydrate.

Glycan

A generic term for any sugar or assembly of sugars in free form or attached to another molecule that is interchangeable with the terms saccharide and carbohydrate.

Mucin

A large, heavily glycosylated protein that is the main component of mucus.

Glycome

Carbohydrates present in a biological sample.

Glycosyltransferases

Enzymes that catalyse the transfer of a sugar from a sugar nucleotide donor to a substrate.

Glycosidases

Enzymes that catalyse the hydrolysis of the bonds between two saccharides in a glycan.

Glycointeractomics

The systematic study of interactions between biological entities mediated by glycans.

Adhesins

A protein on the surface of bacteria, viruses or parasites that binds to a ligand present on the surface of a host cell.

Glycoconjugates

Molecules in which one or more glycan units are covalently linked to a non-carbohydrate entity.

Lewis B

Fucα1-2Galβ1-3(Fucα1-4)GlcNAc, a tetrasaccharide found as a terminal modification on both O-linked and N-linked glycans.

Lewis blood group antigens

A related set of glycans that carry a non-teminal α1-3 or α1-4 fucose residues covalently linked to N-acetylglucosamine.

Sialyl Lewis X

(sLeX). Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAc, a tetrasaccharide found as a terminal modification on both O-linked and N-linked glycans.

Sialyl Lewis A

Neu5Acα2-3Galβ1-3(Fucα1-4)GlcNAc, a tetrasaccharide found as a terminal modification on both O-linked and N-linked glycans.

LacdiNAc

GalNAcβ1-4GlcNAc, a disaccharide found as a terminal modification on both O-linked and N-linked glycans.

MUC5AC

A mucin encoded by the MUC5AC gene.

Group A Streptococcus

(GAS). Streptococcus belonging to the Lancefield grouping based on a serological methodology for classifying Streptococcus species; Streptococcus pyogenes is the species defined by group A Streptococcus.

Glycosaminoglycans

Long unbranched polysaccharides consisting of a repeating disaccharide unit composed of a hexose derivative and an amino sugar derivative that forms the sugar portion of a proteoglycan.

ABO(H) blood group antigens

Carbohydrate structures attached to cells and secreted proteins that determine the blood group and/or type of a person.

Phase variable

A method of responding to varying environments that allows the switching of gene expression in an on–off fashion.

Immunoreceptor tyrosine-based inhibitory motif

(ITIM). A conserved sequence of amino acids found in the cytoplasmic tails of many inhibitory receptors of the immune system.

Group B Streptococcus

(GBS). Streptococcus belonging to the Lancefield grouping based on a serological methodology for classifying Streptococcus species; Streptococcus agalactiae is the species defined by group B Streptococcus.

Oxidative bursts

Release of reactive oxygen species; also known as respiratory bursts.

Neutrophil extracellular traps

Networks of fibres, primarily composed of DNA, used to bind pathogens.

Insertion sequence

(IS). A short (<2500 base pairs) transposable segment of DNA.

N-linked glycosylation

Covalent attachment of a carbohydrate through a bond to the amide nitrogen of an asparagine residue.

O-linked glycosylation

Covalent attachment of a carbohydrate through a bond to the hydroxyl group of a serine or threonine residue.

Nontypeable Haemophilus influenzae

Unencapsulated strains of H. influenzae.

Toll-like receptor-5

A membrane-spanning innate immune system protein known to detect bacterial flagellin.

Type III secretion system

A needle-like structure produced by pathogenic bacteria to deliver proteins to the host cell to facilitate bacterial infection.

Death receptor-mediated apoptosis

Also known as extrinsic apoptosis; programmed cell death activated by immune system signals.

AB5 class toxins

Toxins comprising one A subunit that corrupts critical cell function and five B subunits that direct target cell uptake.

B subunits

Subunits of an AB toxin that are responsible for binding to host cells.

A subunits

Subunits of an AB toxin that are enzymatically active.

Surface plasmon resonance

An optical technique for the measurement of adsorption of materials onto a surface that can estimate affinities of proteins for glycans on coated chips.

Glycomics

Systematic analysis of the glycome.

Isothermal titration calorimetry

A technique that measures the heat released or absorbed during the binding of molecules to determine the binding constants, reaction stoichiometry, enthalpy and entropy of the interaction.

Saturation transfer difference NMR

A NMR technique for determining the interaction between proteins and small molecules by the transfer of magnetic field from the protein to the small molecule.

Anomeric configurations

The bond angle on carbon-1 for most saccharides or carbon-2 for sialic acids (that is, α or β linkage).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Poole, J., Day, C.J., von Itzstein, M. et al. Glycointeractions in bacterial pathogenesis. Nat Rev Microbiol 16, 440–452 (2018). https://doi.org/10.1038/s41579-018-0007-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41579-018-0007-2

This article is cited by

Search

Advanced search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology