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

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 fo