Lipid A is a crucial component of lipopolysaccharide (LPS), a major constituent of the outer membrane of Gram-negative bacteria, including Haemophilus influenzae. It plays a significant role in bacterial pathogenicity and elicits a strong immune response. The biosynthesis of lipid A involves several enzyme-catalyzed steps, with acyltransferases being key enzymes in this process.
The lipid A biosynthesis pathway is well-conserved across Gram-negative bacteria. It involves nine enzyme-catalyzed steps, starting from UDP-N-acetylglucosamine and ending with the mature lipid A molecule. Key enzymes include LpxA, LpxB, LpxC, LpxD, LpxH, LpxK, and WaaA (also known as KdtA) .
KDO (3-deoxy-D-manno-oct-2-ulosonic acid) is a component that links lipid A to the core oligosaccharide of LPS. The presence of KDO is crucial for the biological activity of LPS. In Neisseria meningitidis, KDO-containing lipid A derivatives have been shown to enhance immune responses compared to lipid A alone .
Understanding lipid A biosynthesis and its enzymes can lead to the development of novel antimicrobial strategies. Inhibitors targeting key enzymes in lipid metabolism, such as FabH, have been explored as potential therapeutic agents against Haemophilus influenzae .
| Enzyme | Function |
|---|---|
| LpxA | UDP-N-acetylglucosamine acyltransferase |
| LpxB | Acyltransferase adding the second acyl chain |
| LpxC | Deacetylase |
| LpxD | Acyltransferase adding the third acyl chain |
| LpxH | Dehydratase |
| LpxK | Kinase |
| WaaA | KDO transferase |
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KEGG: hin:HI0199
STRING: 71421.HI0199