Teichoic acids: synthesis and applications

Abstract

This review describes the developments in the synthesis of teichoic acids (TA) - glycosylated poly(alditolphosphates) - and the application of these fragments in immunological studies. These structurally diverse biopolymers are omnipresent constituents of the Gram-positive bacterial cell wall where they fulfill a variety of vital functions. They have been and continue to be attractive synthetic targets because of their challenging structures and the fact that their microheterogeneity precludes their isolation in single and pure enough form from natural sources. Progress in glycosylation chemistry and the development of effective phosphorylation chemistry has driven TA synthesis over the years, and highly complex and large TA structures can now reliably be targeted. Starting from the first TA synthesis in 1981, this review highlights the progress made in the field over the years. The synthesized TA fragments have been used to unravel their role in immunology and it is described how focused libraries of TAs have been used to discover the active principles of the TA polymers that interact with the innate immune system. Recently, synthetic TA fragments have also found applications as well-defined synthetic antigens for the generation of novel vaccine modalities to combat Gram-positive bacterial infections. It is foreseen that synthetic TA fragments will be valuable tools in the future to unravel the mode of action of these biomolecules at the molecular level. They will be instrumental in discovering and characterizing their designated biological binding partners, be it pattern recognition receptors or carbohydrate binding lectins or biomachinery enzymes. This review thus serves to showcase the potential of organic synthesis for (chemical) biology and immunology.

A New Family of Capsule Polymerases Generates Teichoic Acid-Like Capsule Polymers in Gram-Negative Pathogens

“…Literature searches revealed that similar dimeric units are expressed by A. pleuropneumoniae serotypes 1 ( 35 ) and 4 ( 36 ) and by H. influenzae serotype f ( 37 , 38 ). Moreover, in a multitude of bacterial species, one of the hexoses of these dimeric repeating units is replaced by a glycerol, creating a structure similar to that of WTA type II ( 39 , 40 ) ( Fig. 1b ; see also Fig.…”

“…We hypothesized that the additional signals resulted from the fact that the commercially available CDP-glycerol used in the Cps7D and Cps3D reactions was a racemic mixture containing both sn-glycerol-1-phosphate (C2′ of glycerol has S chirality) and sn-glycerol-3-phosphate (C2′ has R chirality; for nomenclature, see reference 40 ). Clearly, both enantiomers are substrates for the enzymes as shown by the complete consumption of CDP-glycerol in the HPLC assay ( Fig.…”

More Than a Pore: A Current Perspective on the In Vivo Mode of Action of the Lipopeptide Antibiotic Daptomycin

“…Undecaprenyl phosphate is not only the carrier molecule for lipid II but also is used to translocate wall teichoic acids (WTAs) over the membrane [114]. It is therefore likely that WTA synthesis is also localized in RIFs.…”

Phosphoglycerol-type wall- and lipoteichoic acids are enantiomeric polymers differentially cleaved by the stereospecific glycerophosphodiesterase GlpQ

“…In some Gram-positive bacteria, including B. subtilis 168 as well as in S. epidermidis and S. lugdunenis , both LTA and WTA are glycerophosphate polymers (17,18,27,28). Nevertheless, they are synthesized by distinct routes (9,10,29). Figure 1 summarizes the biosynthesis pathways of WTA and LTA of B. subtilis 168.…”