Discovery of new biosynthetic pathways: the lipid A story.

Published

Journal Article

The outer monolayer of the outer membrane of Gram-negative bacteria consists of the lipid A component of lipopolysaccharide (LPS), a glucosamine-based saccharolipid that is assembled on the inner surface of the inner membrane. The first six enzymes of the lipid A pathway are required for bacterial growth and are excellent targets for the development of new antibiotics. Following assembly, the ABC transporter MsbA flips nascent LPS to the periplasmic side of the inner membrane, whereupon additional transport proteins direct it to the outer surface of the outer membrane. Depending on the bacterium, various covalent modifications of the lipid A moiety may occur during the transit of LPS to the outer membrane. These extra-cytoplasmic modification enzymes are therefore useful as reporters for monitoring LPS trafficking. Because of its conserved structure in diverse Gram-negative pathogens, lipid A is recognized as foreign by the TLR4/MD2 receptor of the mammalian innate immune system, resulting in rapid macrophage activation and robust cytokine production.

Full Text

Duke Authors

Cited Authors

  • Raetz, CRH; Guan, Z; Ingram, BO; Six, DA; Song, F; Wang, X; Zhao, J

Published Date

  • April 2009

Published In

Volume / Issue

  • 50 Suppl /

Start / End Page

  • S103 - S108

PubMed ID

  • 18974037

Pubmed Central ID

  • 18974037

Electronic International Standard Serial Number (EISSN)

  • 1539-7262

International Standard Serial Number (ISSN)

  • 0022-2275

Digital Object Identifier (DOI)

  • 10.1194/jlr.R800060-JLR200

Language

  • eng