Wall teichoic acid polymers share a common linkage unit, but exhibit structural diversity in their repeat unitsĪ. The phosphodiester-linked polyol repeats extend from the GroP end of the linkage unit ( 91 133). The anomeric phosphate of the linkage unit is covalently attached to peptidoglycan (PG) via a phosphodiester bond to the C6 hydroxyl of N-acetylmuramic acid (MurNAc). The disaccharide linkage unit, which is highly conserved across bacterial species, is comprised of N-acetylmannosamine (β1→4) N-acetylglucosamine-1-phosphate (ManNAc (β1→4) GlcNAc-1P) with one to two glycerol-3-phosphate (GroP) units attached to the C4 oxygen of ManNAc ( 5 71 91). The wall teichoic acid polymer can be divided into two components, a disaccharide linkage unit and a main chain polymer composed of phosphodiester-linked polyol repeat units ( Figure 2) ( 91). aureus WTAs extend well beyond the PG layer ( 81 82 106). Consistent with their estimated length, cryo-EM images suggest that S. The total mass of WTAs in these and other organisms comprises up to 60% of the cell wall ( 44 124). aureus, it has been estimated that every ninth PG MurNAc residue contains an attached WTA polymer containing 40 to 60 polyol repeats ( 12 71). Wall teichoic acids are highly abundant modifications of gram-positive cell walls ( 90). Here we review recent work on WTAs and discuss studies implicating the pathway as a therapeutic target. Due to their importance in pathogenesis, WTAs are possible targets for new therapeutics to overcome resistant bacterial infections.
aureus (MRSA), and they modulate susceptibility to cationic antibiotics in several organisms ( 23 25 144). WTAs are required for β-lactam resistance in methicillin-resistant S. They are intimately involved in many aspects of cell division and are essential for maintaining cell shape in rod-shaped organisms ( 120). Wall teichoic acids (WTAs) are the most abundant PG-linked polymers in many gram-positive organisms ( 91). This PG matrix is essential for survival, and in gram-positive organisms it is densely functionalized with other polymers. Cell envelopes are varied in structure, but all contain layers of peptidoglycan (PG), a crosslinked matrix of linear carbohydrate (glycan) chains linked to one another via covalent bonds between attached peptides ( 130). Bacteria are surrounded by a complex cell envelope that performs a variety of functions ( 114).
0 kommentar(er)
