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  • Review Article
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Teichoic acids and related cell-wall glycopolymers in Gram-positive physiology and host interactions

Nature Reviews Microbiology volume 6, pages 276–287 (2008)Cite this article

Key Points

  • Gram-positive bacteria lack regular outer membranes and instead have thickened peptidoglycan cell walls. Within the fabric of the cell wall, Gram-positive bacteria contain additional cell-wall glycopolymers (CWGs), including at least one membrane-attached (M-CWG) and one peptidoglycan-attached (P-CWG) type. CWG structures are highly diverse and their functions are only partially understood.

  • CWGs differ with regards to their sugar building blocks and non-glycosyl residues. According to net charge, CWGs can be classified into zwitterionic, anionic and uncharged polymers. The classical wall teichoic acids or lipoteichoic acids are zwitterionic because of their negatively charged phosphate and positively charged amino groups (positively charged amino groups are derived in most cases from D-alanine residues). Polyanionic CWGs include, for example, pyruvylated polysaccharides from S-layer-protein-displaying bacilli and their relatives, teichuronic acids and succinylated lipoglycans. Uncharged, often branched CWGs are found, for example, in the cell walls of Mycobacterium tuberculosis and other actinobacteria.

  • Most CWGs seem to have functions in protecting bacterial cell envelopes through the attachment of further protective surface structures, such as S-layer proteins or mycolic acids, or by directly impeding the passage of harmful molecules. Further roles in binding surface proteins and cations, directing the cell-division machinery and enabling biofilm formation by shaping physicochemical surface properties have been described.

  • In addition to bacterial physiology, CWGs can have a range of crucial functions in bacteria–host interactions. These can include: bacterial attachment to host cells, probably through scavenger-receptor-like molecules; induction of proinflammatory responses by Toll-like receptors; activation of complement; and binding of antibodies. Moreover, there is growing evidence that certain zwitterionic glycopolymers can induce major histocompatibility complex class II-dependent activation of T cells, followed by the induction of immunological memory.

  • The pivotal roles of CWGs for Gram-positive viability and/or virulence, together with their easy accessibility, make CWGs promising targets for diagnostics, vaccines and antibiotics. In fact, established diagnostic procedures, such as serological streptococcal differentiation, take advantage of species-specific differences in CWGs. Moreover, promising reports on the use of certain CWGs for active or passive vaccination or of CWG-biosynthetic enzymes as targets for novel antimicrobial compounds indicate the future potential of CWGs for use in new anti-infective strategies.

  • Many topics on CWGs that range from their structural diversity, functions in bacterial physiology and cell division, roles in specific host interactions and usefulness for preventing infections remain major challenges for future research. How CWGs can contribute to bacterial fitness, virulence and host cell tropism, how static or plastic CWG structures are during changing environmental conditions and how CWG biosynthesis is regulated should be investigated more thoroughly using sophisticated glycomics and systems-biology approaches.

Abstract

Abstract | Most Gram-positive bacteria incorporate membrane- or peptidoglycan-attached carbohydrate-based polymers into their cell envelopes. Such cell-wall glycopolymers (CWGs) often have highly variable structures and have crucial roles in protecting, connecting and controlling the major envelope constituents. Further important roles of CWGs in host-cell adhesion, inflammation and immune activation have also been described in recent years. Identifying and harnessing highly conserved or species-specific structural features of CWGs offers excellent opportunities for developing new antibiotics, vaccines and diagnostics for use in the fight against severe infectious diseases, such as sepsis, pneumonia, anthrax and tuberculosis.

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Figure 1: Cell-wall glycopolymers (CWGs) in the cell walls of major human pathogens.
Figure 2: Schematic structures of selected cell-wall glycopolymers (CWGs).
Figure 3: Roles of wall teichoic acid (WTA) and lipoteichoic acid (LTA) in the cell wall of Staphylococcus aureus.
Figure 4: Interaction of cell-wall glycopolymers (CWGs) with host molecules.

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Acknowledgements

The authors thank J. Lee, E. Kannenberg and J. Kokai-Kun for helpful discussions and H. Hölscher for critically reading the manuscript. A.P. is supported by grants from the German Research Foundation (TR-SFB34, FOR449, GRK685, SFB766 and SFB685), the European Union (LSHM-CT-2004-512093), the German Ministry of Education and Research (NGFN2 and SKINSTAPH) and the IZKF programme of the Medical Faculty, University of Tübingen. C.W. is supported by grants from the German Research Foundation (WE 4291/1-1 and SPP1130).

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    Christopher Weidenmaier & Andreas Peschel

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DATABASES

Entrez Genome Project

Bacillus anthracis

Bacillus subtilis

Bacteroides fragilis

Clostridium difficile

Enterococcus faecalis

Lactococcus garvieae

Listeria monocytogenes

Micrococcus luteus

Mycobacterium avium

Mycobacterium bovis

Mycobacterium tuberculosis

Staphylococcus aureus

Staphylococcus epidermidis

Streptococcus agalactiae

Streptococcus gordonii

Streptococcus pneumoniae

Streptococcus pyogenes

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Glossary

Capsular polysaccharide

A glycopolymer, usually of variable composition and structure, that forms capsule-like protective layers around microbial cells.

S-layer protein

Forms a crystalline two-dimensional lattice on microbial-cell surfaces.

Mycolic acid

Very-long-chain fatty acid that contains up to 60 carbon atoms and unusual modifications that form an outer-membrane-like layer on the surface of mycobacteria and their relatives. Mycolic acids are responsible for mycobacterial surface hydrophobicity and resistance to most conventional antibiotics.

Teichoic acid

A cell-envelope glycopolymer that is composed of many identical sugar-phosphate repeating units, which are usually modified with d-alanine and additional sugars.

Lipoteichoic acid (LTA)

A teichoic acid species that is connected to membrane glycolipids. The stereochemistry of LTAs and the biosynthetic origin of the glycerolphosphates are different from those of wall teichoic acids, which have glycerol-phosphate backbones.

Teichuronic acid

A teichoic acid-like polymer that lacks phosphate groups and possesses polyanionic properties because of the presence of uronic acid-containing repeating units.

Uronic acid

A sugar-derived acid, such as glucuronic acid or galacturonic acid.

Zwitterionic

The occurrence of both negatively and positively charged groups in a molecule.

Bacteriocin

A bacterially produced, small, heat-stable peptide that is active against other bacteria and to which the producer has a specific immunity mechanism. Bacteriocins can have a narrow or broad target spectrum.

Defensin

A cationic peptide that is produced by the innate immune system, and kills bacteria, for example, by disrupting the phospholipid bilayer.

Pathogen-associated molecular pattern

A small molecular motif that is conserved across microbial species and engages innate immune receptors (for example, Toll-like receptors).

Pattern-recognition receptor

A host receptor (such as a Toll-like receptor) that can sense pathogen-associated molecular patterns and initiate signalling cascades that lead to an innate immune response.

Type I transmembrane protein

A protein which contains a single membrane-spanning domain that has its carboxyl terminus orientated towards the cytoplasm and its amino terminus orientated towards the lumen of membrane compartments or in an extracellular direction.

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Weidenmaier, C., Peschel, A. Teichoic acids and related cell-wall glycopolymers in Gram-positive physiology and host interactions. Nat Rev Microbiol 6, 276–287 (2008). https://doi.org/10.1038/nrmicro1861

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