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