PMID- 24838025
OWN - NLM
STAT- MEDLINE
DCOM- 20161103
LR  - 20220409
IS  - 1469-185X (Electronic)
IS  - 1464-7931 (Print)
IS  - 0006-3231 (Linking)
VI  - 90
IP  - 2
DP  - 2015 May
TI  - Kdo2 -lipid A: structural diversity and impact on immunopharmacology.
PG  - 408-27
LID - 10.1111/brv.12114 [doi]
AB  - 3-deoxy-d-manno-octulosonic acid-lipid A (Kdo2 -lipid A) is the essential 
      component of lipopolysaccharide in most Gram-negative bacteria and the minimal 
      structural component to sustain bacterial viability. It serves as the active 
      component of lipopolysaccharide to stimulate potent host immune responses through 
      the complex of Toll-like-receptor 4 (TLR4) and myeloid differentiation protein 2. 
      The entire biosynthetic pathway of Escherichia coli Kdo2 -lipid A has been 
      elucidated and the nine enzymes of the pathway are shared by most Gram-negative 
      bacteria, indicating conserved Kdo2 -lipid A structure across different species. 
      Yet many bacteria can modify the structure of their Kdo2 -lipid A which serves as 
      a strategy to modulate bacterial virulence and adapt to different growth 
      environments as well as to avoid recognition by the mammalian innate immune 
      systems. Key enzymes and receptors involved in Kdo2 -lipid A biosynthesis, 
      structural modification and its interaction with the TLR4 pathway represent a 
      clear opportunity for immunopharmacological exploitation. These include the 
      development of novel antibiotics targeting key biosynthetic enzymes and 
      utilization of structurally modified Kdo2 -lipid A or correspondingly engineered 
      live bacteria as vaccines and adjuvants. Kdo2 -lipid A/TLR4 antagonists can also 
      be applied in anti-inflammatory interventions. This review summarizes recent 
      knowledge on both the fundamental processes of Kdo2 -lipid A biosynthesis, 
      structural modification and immune stimulation, and applied research on 
      pharmacological exploitations of these processes for therapeutic development.
CI  - (c) 2014 The Authors. Biological Reviews published by John Wiley & Sons Ltd on 
      behalf of Cambridge Philosophical Society.
FAU - Wang, Xiaoyuan
AU  - Wang X
AD  - State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 
      Lihu Avenue, Wuxi 214122, China; Synergetic Innovation Center of Food Safety and 
      Nutrition, Jiangnan University, Wuxi, China.
FAU - Quinn, Peter J
AU  - Quinn PJ
FAU - Yan, Aixin
AU  - Yan A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20140516
PL  - England
TA  - Biol Rev Camb Philos Soc
JT  - Biological reviews of the Cambridge Philosophical Society
JID - 0414576
RN  - 0 (Lipid A)
RN  - 0 (Toll-Like Receptor 4)
RN  - 143600-83-3 (3-deoxy-2-octulosonic acid(2)-lipid IV(A))
SB  - IM
MH  - Gene Expression Regulation, Bacterial/*physiology
MH  - Gram-Negative Bacteria/*enzymology/metabolism
MH  - Lipid A/*analogs & derivatives/biosynthesis/chemistry/genetics/metabolism
MH  - Toll-Like Receptor 4
PMC - PMC4402001
OTO - NOTNLM
OT  - Gram-negative bacteria
OT  - Kdo2-lipid A
OT  - endotoxin
OT  - lipopolysaccharide
OT  - outer membrane
EDAT- 2014/05/20 06:00
MHDA- 2016/11/04 06:00
PMCR- 2015/04/18
CRDT- 2014/05/20 06:00
PHST- 2013/11/10 00:00 [received]
PHST- 2014/04/10 00:00 [revised]
PHST- 2014/04/17 00:00 [accepted]
PHST- 2014/05/20 06:00 [entrez]
PHST- 2014/05/20 06:00 [pubmed]
PHST- 2016/11/04 06:00 [medline]
PHST- 2015/04/18 00:00 [pmc-release]
AID - 10.1111/brv.12114 [doi]
PST - ppublish
SO  - Biol Rev Camb Philos Soc. 2015 May;90(2):408-27. doi: 10.1111/brv.12114. Epub 
      2014 May 16.