Location, synthesis and function of glycolipids and polyglycerolphosphate lipoteichoic acid in Gram-positive bacteria of the phylum Firmicutes

Abstract

Lipoteichoic acid (LTA) is a zwitterionic polymer found in the cell wall of many Gram-positive bacteria. A widespread and one of the best-studied forms of LTA consists of a polyglycerolphosphate (PGP) chain that is tethered to the membrane via a glycolipid anchor. In this review, we will summarize our current understanding of the enzymes involved in glycolipid and PGP backbone synthesis in a variety of different Gram-positive bacteria. The recent identification of key LTA synthesis proteins allowed the construction and analysis of mutant strains with defined defects in glycolipid or backbone synthesis. Using these strains, new information on the functions of LTA for bacterial growth, physiology and during developmental processes was gained and will be discussed. Furthermore, we will reintroduce the idea that LTA remains in close proximity to the bacterial membrane for its function during bacterial growth rather than as a surface-exposed structure.

A Bifunctional Glycosyltransferase from Agrobacterium tumefaciens Synthesizes Monoglucosyl and Glucuronosyl Diacylglycerol under Phosphate Deprivation

“…It represents a bulk lipid in these organisms. MGlcD (with ␣-or ␤-anomeric configuration) is also found in many Gram-positive bacteria (1), often building the precursor for the synthesis of DGlcD (2).…”

“…Glycolipids are characterized by a high headgroup diversity, which is determined by the number and type of sugars (glucose, galactose, mannose, or charged sugars like glucuronic acid or sulfoquinovose) with different anomeric configurations (␣ and ␤) and linkages to each other (132, 133, 134, and 136). In Gram-positive bacteria, glycolipids represent building blocks for membranes or serve as membrane anchors for lipoteichoic acids (1,2). Glycolipids also play an important role in several members of Gram-negative bacteria (Proteobacteria) under phosphate deprivation, similar to plants and cyanobacteria, where they replace phospholipids to save phosphate required for the synthesis of phosphate-containing metabolites (1,3,4).…”

“…Besides glycolipids, further phosphate-free lipids are often involved in this physiological stress response in bacteria (5). Two representatives of such nonphospholipids are diacylglyceryl trimethylhomoserine (DGTS) 2 or the glycerol-free ornithine lipid (OL).…”

“…Irrespective of the high variety of bacterial glycolipids, only a few lipid glycosyltransferases have been cloned so far (1,2). The best studied glycosyltransferases synthesizing monoglucosyl diacylglycerol (MGlcD) and diglucosyl diacylglycerol (DGlcD), with all sugars bound in ␣-anomeric configuration, were isolated from cell wall-less bacterium Acholeplasma laidlawii (7).…”

Small molecule inhibitor of lipoteichoic acid synthesis is an antibiotic for Gram-positive bacteria

“…Gram-positive bacteria incorporate lipoteichoic acids (LTAs) into their envelope to scavenge magnesium ions, direct autolysins to subcellular cell wall locations, and enable bacterial cell division (6,7). LTA from S. aureus and other bacteria is composed of 1,3-polyglycerol-phosphate linked to glycolipid, which provides for LTA anchoring in membranes (8).…”