Lipopolysaccharide Endotoxins

Overview

Journal Annu Rev Biochem

Publisher Annual Reviews

Specialty Biochemistry

Date 2002 Jun 5

PMID 12045108

Citations 1846

Authors

Christian R H Raetz

Chris Whitfield

Affiliations

Soon will be listed here.

Abstract

Bacterial lipopolysaccharides (LPS) typically consist of a hydrophobic domain known as lipid A (or endotoxin), a nonrepeating "core" oligosaccharide, and a distal polysaccharide (or O-antigen). Recent genomic data have facilitated study of LPS assembly in diverse Gram-negative bacteria, many of which are human or plant pathogens, and have established the importance of lateral gene transfer in generating structural diversity of O-antigens. Many enzymes of lipid A biosynthesis like LpxC have been validated as targets for development of new antibiotics. Key genes for lipid A biosynthesis have unexpectedly also been found in higher plants, indicating that eukaryotic lipid A-like molecules may exist. Most significant has been the identification of the plasma membrane protein TLR4 as the lipid A signaling receptor of animal cells. TLR4 belongs to a family of innate immunity receptors that possess a large extracellular domain of leucine-rich repeats, a single trans-membrane segment, and a smaller cytoplasmic signaling region that engages the adaptor protein MyD88. The expanding knowledge of TLR4 specificity and its downstream signaling pathways should provide new opportunities for blocking inflammation associated with infection.

Citing Articles

The Absence of a Very Long Chain Fatty Acid (VLCFA) in Lipid A Impairs Plant Infection and Biofilm Formation and Increases Susceptibility to Environmental Stressors.

Komaniecka I, Zebracki K, Mazur A, Susniak K, Sroka-Bartnicka A, Swatek A Molecules. 2025; 30(5).

PMID: 40076305 PMC: 11901934. DOI: 10.3390/molecules30051080.

Linoleic acid inhibits lipopolysaccharide-induced inflammation by promoting TLR4 regulated autophagy in murine RAW264.7 macrophages.

Qin Y, Li K, Zhang Q, Liu J, Xie Y, Zhang T J Appl Biomed. 2025; 22(4):185-196.

PMID: 40033806 DOI: 10.32725/jab.2024.023.

Macrophage pyroptosis and its crucial role in ALI/ARDS.

Cai Y, Shang L, Zhou F, Zhang M, Li J, Wang S Front Immunol. 2025; 16:1530849.

PMID: 40028334 PMC: 11867949. DOI: 10.3389/fimmu.2025.1530849.

Significant Association Between Increased Abundance of Selected Bacterial Lipopolysaccharides and Norovirus Diarrhea Among South African Infants.

Kgosana L, Seheri M, Magwira C Viruses. 2025; 17(2).

PMID: 40007033 PMC: 11860319. DOI: 10.3390/v17020278.

Role of Gene in Physiology and Pathogenicity of .

Che J, Liu B, Fang Q, Hu S, Wang L, Bao B Microorganisms. 2025; 13(2).

PMID: 40005752 PMC: 11857884. DOI: 10.3390/microorganisms13020386.

References

Nummila K, Kilpelainen I, Zahringer U, Vaara M, Helander I . Lipopolysaccharides of polymyxin B-resistant mutants of Escherichia coli are extensively substituted by 2-aminoethyl pyrophosphate and contain aminoarabinose in lipid A. Mol Microbiol. 1995; 16(2):271-8. DOI: 10.1111/j.1365-2958.1995.tb02299.x. View

Jansson P, Lonngren J, Widmalm G, Leontein K, Slettengren K, Svenson S . Structural studies of the O-antigen polysaccharides of Klebsiella O5 and Escherichia coli O8. Carbohydr Res. 1985; 145(1):59-66. DOI: 10.1016/s0008-6215(00)90412-9. View

NIKAIDO K, Nikaido H . Glucosylation of lipopolysaccharide in Salmonella: biosynthesis nof O antigen factor n12 2 . II. Structure of the lipid intermediate. J Biol Chem. 1971; 246(12):3912-9. View

Gibb A, Barclay G, Poxton I, Di Padova F . Frequencies of lipopolysaccharide core types among clinical isolates of Escherichia coli defined with monoclonal antibodies. J Infect Dis. 1992; 166(5):1051-7. DOI: 10.1093/infdis/166.5.1051. View

Kahler C, Stephens D . Genetic basis for biosynthesis, structure, and function of meningococcal lipooligosaccharide (endotoxin). Crit Rev Microbiol. 1999; 24(4):281-334. DOI: 10.1080/10408419891294216. View

Belunis C, Mdluli K, Raetz C, Nano F . A novel 3-deoxy-D-manno-octulosonic acid transferase from Chlamydia trachomatis required for expression of the genus-specific epitope. J Biol Chem. 1992; 267(26):18702-7. View

Kelly R, Whitfield C . Clonally diverse rfb gene clusters are involved in expression of a family of related D-galactan O antigens in Klebsiella species. J Bacteriol. 1996; 178(17):5205-14. PMC: 178318. DOI: 10.1128/jb.178.17.5205-5214.1996. View

Zhou Z, Ribeiro A, Lin S, Cotter R, MILLER S, Raetz C . Lipid A modifications in polymyxin-resistant Salmonella typhimurium: PMRA-dependent 4-amino-4-deoxy-L-arabinose, and phosphoethanolamine incorporation. J Biol Chem. 2001; 276(46):43111-21. DOI: 10.1074/jbc.M106960200. View

Que N, Ribeiro A, Raetz C . Two-dimensional NMR spectroscopy and structures of six lipid A species from Rhizobium etli CE3. Detection of an acyloxyacyl residue in each component and origin of the aminogluconate moiety. J Biol Chem. 2000; 275(36):28017-27. PMC: 2570648. DOI: 10.1074/jbc.M004009200. View

10.

PATCHETT A, CORDES E . The design and properties of N-carboxyalkyldipeptide inhibitors of angiotensin-converting enzyme. Adv Enzymol Relat Areas Mol Biol. 1985; 57:1-84. DOI: 10.1002/9780470123034.ch1. View

11.

Ferguson A, Welte W, Hofmann E, Lindner B, Holst O, Coulton J . A conserved structural motif for lipopolysaccharide recognition by procaryotic and eucaryotic proteins. Structure. 2000; 8(6):585-92. DOI: 10.1016/s0969-2126(00)00143-x. View

12.

de Cock H, Brandenburg K, Wiese A, Holst O, Seydel U . Non-lamellar structure and negative charges of lipopolysaccharides required for efficient folding of outer membrane protein PhoE of Escherichia coli. J Biol Chem. 1999; 274(8):5114-9. DOI: 10.1074/jbc.274.8.5114. View

13.

Schumann R, Leong S, Flaggs G, Gray P, Wright S, Mathison J . Structure and function of lipopolysaccharide binding protein. Science. 1990; 249(4975):1429-31. DOI: 10.1126/science.2402637. View

14.

Price N, Kelly T, Raetz C, Carlson R . Biosynthesis of a structurally novel lipid A in Rhizobium leguminosarum: identification and characterization of six metabolic steps leading from UDP-GlcNAc to 3-deoxy-D-manno-2-octulosonic acid2-lipid IVA. J Bacteriol. 1994; 176(15):4646-55. PMC: 196286. DOI: 10.1128/jb.176.15.4646-4655.1994. View

15.

Trent M, Ribeiro A, Doerrler W, Lin S, Cotter R, Raetz C . Accumulation of a polyisoprene-linked amino sugar in polymyxin-resistant Salmonella typhimurium and Escherichia coli: structural characterization and transfer to lipid A in the periplasm. J Biol Chem. 2001; 276(46):43132-44. DOI: 10.1074/jbc.M106962200. View

16.

Crowell D, Anderson M, Raetz C . Molecular cloning of the genes for lipid A disaccharide synthase and UDP-N-acetylglucosamine acyltransferase in Escherichia coli. J Bacteriol. 1986; 168(1):152-9. PMC: 213431. DOI: 10.1128/jb.168.1.152-159.1986. View

17.

Whitfield C, Richards J, Perry M, Clarke B, Maclean L . Expression of two structurally distinct D-galactan O antigens in the lipopolysaccharide of Klebsiella pneumoniae serotype O1. J Bacteriol. 1991; 173(4):1420-31. PMC: 207279. DOI: 10.1128/jb.173.4.1420-1431.1991. View

18.

Feldman M, Marolda C, Monteiro M, Perry M, Parodi A, Valvano M . The activity of a putative polyisoprenol-linked sugar translocase (Wzx) involved in Escherichia coli O antigen assembly is independent of the chemical structure of the O repeat. J Biol Chem. 1999; 274(49):35129-38. DOI: 10.1074/jbc.274.49.35129. View

19.

van der Ley P, Steeghs L, Hamstra H, Ten Hove J, Zomer B, van Alphen L . Modification of lipid A biosynthesis in Neisseria meningitidis lpxL mutants: influence on lipopolysaccharide structure, toxicity, and adjuvant activity. Infect Immun. 2001; 69(10):5981-90. PMC: 98725. DOI: 10.1128/IAI.69.10.5981-5990.2001. View

20.

Burns S, Hull S . Comparison of loss of serum resistance by defined lipopolysaccharide mutants and an acapsular mutant of uropathogenic Escherichia coli O75:K5. Infect Immun. 1998; 66(9):4244-53. PMC: 108512. DOI: 10.1128/IAI.66.9.4244-4253.1998. View