Discovery of new biosynthetic pathways: the lipid A story
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 g...
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doaj-b6d9c52c6b2e4c9783d1fcf8e7cc54c62021-04-28T05:55:46ZengElsevierJournal of Lipid Research0022-22752009-01-0150S103S108Discovery of new biosynthetic pathways: the lipid A storyChristian R.H. Raetz0Ziqiang Guan1Brian O. Ingram2David A. Six3Feng Song4Xiaoyuan Wang5Jinshi Zhao6To whom correspondence should be addressed; Department of Biochemistry, Duke University Medical Center, P.O. Box 3711, Durham, NC 27710Department of Biochemistry, Duke University Medical Center, P.O. Box 3711, Durham, NC 27710Department of Biochemistry, Duke University Medical Center, P.O. Box 3711, Durham, NC 27710Department of Biochemistry, Duke University Medical Center, P.O. Box 3711, Durham, NC 27710Department of Biochemistry, Duke University Medical Center, P.O. Box 3711, Durham, NC 27710Department of Biochemistry, Duke University Medical Center, P.O. Box 3711, Durham, NC 27710Department of Biochemistry, Duke University Medical Center, P.O. Box 3711, Durham, NC 27710The 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.http://www.sciencedirect.com/science/article/pii/S0022227520305952Francisella tularensisendotoxinvaccine adjuvant |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christian R.H. Raetz Ziqiang Guan Brian O. Ingram David A. Six Feng Song Xiaoyuan Wang Jinshi Zhao |
spellingShingle |
Christian R.H. Raetz Ziqiang Guan Brian O. Ingram David A. Six Feng Song Xiaoyuan Wang Jinshi Zhao Discovery of new biosynthetic pathways: the lipid A story Journal of Lipid Research Francisella tularensis endotoxin vaccine adjuvant |
author_facet |
Christian R.H. Raetz Ziqiang Guan Brian O. Ingram David A. Six Feng Song Xiaoyuan Wang Jinshi Zhao |
author_sort |
Christian R.H. Raetz |
title |
Discovery of new biosynthetic pathways: the lipid A story |
title_short |
Discovery of new biosynthetic pathways: the lipid A story |
title_full |
Discovery of new biosynthetic pathways: the lipid A story |
title_fullStr |
Discovery of new biosynthetic pathways: the lipid A story |
title_full_unstemmed |
Discovery of new biosynthetic pathways: the lipid A story |
title_sort |
discovery of new biosynthetic pathways: the lipid a story |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2009-01-01 |
description |
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. |
topic |
Francisella tularensis endotoxin vaccine adjuvant |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520305952 |
work_keys_str_mv |
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