A Journey from Structure to Function of Bacterial Lipopolysaccharides

Abstract

Lipopolysaccharide (LPS) is a crucial constituent of the outer membrane of most Gram-negative bacteria, playing a fundamental role in the protection of bacteria from environmental stress factors, in drug resistance, in pathogenesis, and in symbiosis. During the last decades, LPS has been thoroughly dissected, and massive information on this fascinating biomolecule is now available. In this Review, we will give the reader a third millennium update of the current knowledge of LPS with key information on the inherent peculiar carbohydrate chemistry due to often puzzling sugar residues that are uniquely found on it. Then, we will drive the reader through the complex and multifarious immunological outcomes that any given LPS can raise, which is strictly dependent on its chemical structure. Further, we will argue about issues that still remain unresolved and that would represent the immediate future of LPS research. It is critical to address these points to complete our notions on LPS chemistry, functions, and roles, in turn leading to innovative ways to manipulate the processes involving such a still controversial and intriguing biomolecule.

Polymyxin B1 within the E. coli cell envelope: insights from molecular dynamics simulations

“…The precise composition of both leaflets varies depending on the bacterial species. (Sohlenkamp and Geiger 2016;Di Lorenzo et al 2021) LPS is a complex glycolipid consisting of a lipid A moiety (with 4-6 acyl tails) attached to an oligosaccharide core, which may be attached to a highly variable O-antigen polysaccharide (Fig. 1C).…”

The Unusual Lipid A Structure and Immunoinhibitory Activity of LPS from Marine Bacteria Echinicola pacifica KMM 6172T and Echinicola vietnamensis KMM 6221T

“…Marine bacteria are predominantly Gram-negative; therefore, their cell envelope has a 3-layered architecture consisting of a cytoplasmic membrane, a periplasmic space containing the peptidoglycan layer and soluble proteins, and an outer membrane whose exterior leaflet is covered by lipopolysaccharides (LPS) [3][4][5]. LPS are typically made up of three different constituents: a glycolipid anchor to the outer membrane, the lipid A, an oligosaccharide (core OS), and a polysaccharide portion (O-chain), which is the outermost part of the whole molecule.…”

“…LPS are typically made up of three different constituents: a glycolipid anchor to the outer membrane, the lipid A, an oligosaccharide (core OS), and a polysaccharide portion (O-chain), which is the outermost part of the whole molecule. An LPS expressing all three domains is denominated a smoothtype LPS (S-LPS); whereas, when the O-chain portion is missing it is named rough-type LPS (R-LPS or LOS) [4][5][6]. Due to their external location, LPS are involved in several biological activities ranging from membrane stabilization to the defense against dangerous outside agents [4][5][6].…”

“…An LPS expressing all three domains is denominated a smoothtype LPS (S-LPS); whereas, when the O-chain portion is missing it is named rough-type LPS (R-LPS or LOS) [4][5][6]. Due to their external location, LPS are involved in several biological activities ranging from membrane stabilization to the defense against dangerous outside agents [4][5][6]. Nevertheless, LPS are certainly known for their central role in many aspects of host-microbe interaction events, such as, among others, colonization, symbiosis, and virulence [3][4][5][6].…”

“…Due to their external location, LPS are involved in several biological activities ranging from membrane stabilization to the defense against dangerous outside agents [4][5][6]. Nevertheless, LPS are certainly known for their central role in many aspects of host-microbe interaction events, such as, among others, colonization, symbiosis, and virulence [3][4][5][6]. For bacteria that interact with humans, in fact, LPS is recognized by the innate immunity receptor complex built up of Toll-like receptor 4 (TLR4) and myeloid differentiation factor-2 (MD-2), which is located on several types of immune cells.…”