Lipopolysaccharides of Gram-Negative Bacteria: Biosynthesis and Structural Aspects

Abstract

Gram-negative bacteria are to a large extent covered by lipopolysaccharide (LPS) anchored in the outer leaflet of their outer membrane. There are presently four described pathways for the O-antigen assembly of LPS, viz., synthase-, Wzk-, ABC-transporterand Wzx/Wzy-dependent pathways, where the latter two are used in Escherichia coli, subject to the O-antigen polysaccharide to be made. NDP-sugar monosaccharides are used by glycosyltransferases in the process of linking sugar residues together in the cytoplasm and depending on the biosynthetic pathway polymerization of the O-antigen takes place either in the cytoplasm (ABCtransporter pathway) or in the periplasm, where an oligosaccharide anchored in the inner membrane is flipped to the periplasmic side to this end (Wzx/Wzy-dependent pathway). Additions of sugars to form side-chains on the O-antigen may also occur in the periplasmic space. The degree of polymerization of the O-antigen is regulated to give a modal distribution, i.e., a narrow distribution around the most probable chain-length. The O-antigen is subsequently conjugated to the lipid A-core to form the LPS, which is transported across the periplasmic region by an ATP-driven mechanism as part of an LPS transport (Lpt) system. By using predictions of NDPmonosaccharide pathways and glycosyltransferase function it is shown how O-antigen structure can be elucidated rapidly by the computer program CASPER using bioinformatics data in conjunction with unassigned NMR data of the polysaccharide.For the bacterium the LPS acts as an effective permeability barrier to cationic antimicrobial peptides, enhances intracellular survival and contributes to the evasion of the immune defenses by mimicry of host molecules (16).An LPS molecule is a lipoglycan and contains three structural GLYCO REVIEW

Nucleotide Sugars in Chemistry and Biology

“…Bacteria have developed different types of cell envelope architectures for protection. The cell envelope of Gram-positive bacteria consists of one lipid bilayer and a thick peptidoglycan layer, whereas in Gram-negative bacteria, there are two lipid bilayers and a thinner peptidoglycan in between them [38,39]. The carbohydrate component of peptidoglycan is an oligosaccharide consisting of alternating N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) residues, which are both derived from UDP-GlcNAc [40,41].…”

“…Oligosaccharides are crosslinked by oligopeptides attached to MurNAc residues, and a mesh-like structure is formed. The cell-surface is decorated with glycoconjugates, such as wall teichoic acids and lipoteichoic acids in Gram-positive bacteria [20,[42][43][44] and lipopolysaccharides in Gram-negative bacteria [39,45,46]. Both Gram-negative and Gram-positive bacteria can be further protected by a capsule that consists of oligosaccharides [21,23,43,[47][48][49][50].…”

Influences of Vibrio cholerae Lipid A Types on LPS Bilayer Properties

“…1 The LPS molecule can be subdivided into lipid A, core oligosaccharide, and O-antigen polysaccharide. 2 Vibrio cholerae (V. cholerae) is a Gramnegative bacterium causing diseases of water acute diarrhea and rapid dehydration that could kill a person in a few hours. 3 Each year alone, several million people are infected by V. cholerae that is also responsible for ∼100 000 deaths.…”

“…A characteristic feature of Gram-negative bacteria is the presence of a highly asymmetric outer membrane composed of glycerophospholipids in the inner leaflet and lipopolysaccharides (LPS) in the outer leaflet . The LPS molecule can be subdivided into lipid A, core oligosaccharide, and O-antigen polysaccharide .…”

CHARMM-GUI Supports Hydrogen Mass Repartitioning and Different Protonation States of Phosphates in Lipopolysaccharides

“…LPS molecules, which are found in the outer leaflet of the outer membranes (OM) of Gram-negative bacteria, are composed of lipid A, core oligosaccharide, and O-antigen polysaccharide, representing one of the most complex biological molecules. , In LPS, phosphate groups are often attached to the glucosamine dimer of lipid A and l -glycero- d -manno-heptose (Hep) of a core oligosaccharide. At 25 °C, two p K a values of glucose-1-phosphate and glucose-4-phosphate are 1.10/6.13 and 0.84/5.67, respectively. , Under physiological conditions, however, the protonation states, either −2 e or −1 e , of phosphate groups in LPS are difficult to be determined unambiguously due to unknown pH at the bacterial OM surface.…”