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Lipopolysaccharides: regulated biosynthesis and structural diversity

Abstract

The cell envelope of Gram-negative bacteria contains two distinct membranes, an inner (IM) and an outer (OM) membrane, separated by the periplasm, a hydrophilic compartment that includes a thin layer of peptidoglycan. The most distinguishing feature of such bacteria is the presence of an asymmetric OM with phospholipids located in the inner leaflet and lipopolysaccharides (LPSs) facing the outer leaflet. The maintenance of this OM asymmetry is essential to impart a permeability barrier, which prevents the entry of bulky toxic molecules, such as antibiotics and bile salts, into the cells [1]. LPS is a complex glycolipid that, with few exceptions, is essential for bacterial viability and is one of the major virulence factors in pathogenic Gram-negative bacteria. Model bacteria, such as Escherichia coli, contain approximately 2–3 × 106 molecules of LPS that cover more than 75% of the OM [2]. The composition of LPS is highly heterogenous; however, they often share a common architecture, and for convenience can be divided into three parts. The first, a conserved glycophospholipid moiety called lipid A, which anchors LPS in the OM, constitutes the endotoxin principal since it is recognized by the innate immune cell receptor TLR4/MD2-CD14 complex. A proximal core oligosaccharide is attached to lipid A via 3-deoxy-α-D-manno-oct-2-ulsonic acid (Kdo), and in smooth bacteria a distal O-polysaccharide called an O-antigen is attached [3]. It should be noted that some bacteria display LPSs without the O-chain, which are thus named lipooligosaccharides (LOSs). The biosynthesis of LPS begins with the formation of the essential key precursor molecule Kdo2-lipid A, which requires the sequential action of seven essential enzymes on the cytoplasmic side of the IM. This Kdo2-lipid A serves as a substrate for an extension by the incorporation of various sugars by specific glycosyltransferases before the lipid A-core molecules are flipped by MsbA to the periplasmic side of the IM.

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Keywords

Details

Category:
Articles
Type:
artykuły w czasopismach
Published in:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES no. 24,
ISSN: 1661-6596
Language:
English
Publication year:
2023
Bibliographic description:
Raina S.: Lipopolysaccharides: regulated biosynthesis and structural diversity// INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES -Vol. 24,iss. 8 (2023), s.7498-
DOI:
Digital Object Identifier (open in new tab) 10.3390/ijms24087498
Sources of funding:
Verified by:
Gdańsk University of Technology

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