A Continuum of Anionic Charge: Structures and Functions ofd-Alanyl-Teichoic Acids in Gram-Positive Bacteria

Abstract

SUMMARY Teichoic acids (TAs) are major wall and membrane components of most gram-positive bacteria. With few exceptions, they are polymers of glycerol-phosphate or ribitol-phosphate to which are attached glycosyl and d-alanyl ester residues. Wall TA is attached to peptidoglycan via a linkage unit, whereas lipoteichoic acid is attached to glycolipid intercalated in the membrane. Together with peptidoglycan, these polymers make up a polyanionic matrix that functions in (i) cation homeostasis; (ii) trafficking of ions, nutrients, proteins, and antibiotics; (iii) regulation of autolysins; and (iv) presentation of envelope proteins. The esterification of TAs with d-alanyl esters provides a means of modulating the net anionic charge, determining the cationic binding capacity, and displaying cations in the wall. This review addresses the structures and functions of d-alanyl-TAs, the d-alanylation system encoded by the dlt operon, and the roles of TAs in cell growth. The importance of dlt in the physiology of many organisms is illustrated by the variety of mutant phenotypes. In addition, advances in our understanding of d-alanyl ester function in virulence and host-mediated responses have been made possible through targeted mutagenesis of dlt. Studies of the mechanism of d-alanylation have identified two potential targets of antibacterial action and provided possible screening reactions for designing novel agents targeted to d-alanyl-TA synthesis.

Structural investigation of humanS. aureus-targeting antibodies that bind wall teichoic acid

“…To our knowledge, our structures are the first atomic descriptions of antibodies in complex with an epitope from the Gram-positive restricted teichoic acid family of polysaccharides. Wall teichoic acid is a major component of the cell wall structure of S. aureus , 39 and along with PNAG 22 and the glycosylated SD repeats (SDRs) of adhesive factors such as ClfA, 8 is a key exposed epitope on the surface of the bacteria. Importantly, we showed by immunoradiometric assay that each S. aureus cell exposes between 20,000 and 30,000 binding sites for each of our anti-WTA antibodies (Figure 3), highlighting the abundance of the WTA epitope at the S. aureus surface.…”

Hydrolysis of peptidoglycan is modulated by amidation of meso‐diaminopimelic acid and Mg2+ in Bacillus subtilis

“…Gram‐positive cell walls further contain carbohydrate‐based anionic polymers, primarily teichoic acids, which account for roughly half of the mass of the cell wall. Their physiological functions remain elusive but they play a major role in divalent cation binding (particularly Mg 2+ ) (Brown et al ., 2013; Neuhaus and Baddiley, 2003; Heckels et al ., 1977), they serve as scaffolds for a wide range of molecules and they regulate cell wall‐associated enzymes (Yamamoto et al ., 2008; Brown et al ., 2013). …”

Lactobacillus plantarum Lipoteichoic Acid Alleviates TNF-α-Induced Inflammation in the HT-29 Intestinal Epithelial Cell Line

“…Although both pathogenic and probiotic Gram-positive bacteria express LTA (Neuhaus and Baddiley, 2003), the immunomodulatory properties of the two types are very different. LTAs from pathogenic Gram-positive bacteria such as S. aureus, S. pneumonia, and S. epidermidis, efficiently activate monocytes and macrophages through the secretion of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-8 (Ellingsen et al, 2002;Mattsson et al, 1993;Standiford et al, 1994).…”