Pseudomonas aeruginosa lipid A diversity and its recognition by Toll-like receptor 4.

Abstract

Lipid A is the pro-inflammatory component of bacterial lipopolysaccharide, the major surface component of Gram-negative bacteria. Gram-negative bacteria alter the structure of lipid A in response to specific environmental conditions including those found upon colonization of a host. The opportunistic pathogen Pseudomonas aeruginosa synthesizes a unique hexa-acylated lipid A containing palmitate and aminoarabinose during adaptation to the cystic fibrosis airway. Different lipid A species are observed in P. aeruginosa isolated from non-cystic fibrosis associated infections. Here we report that P. aeruginosa isolates from the airway of a cystic fibrosis patient with severe pulmonary disease synthesized a novel hepta-acylated lipid A. Cystic fibrosis-specific P. aeruginosa lipid A modifications result in resistance to host antimicrobial peptides and increased recognition by human Toll-like receptor 4 (TLR4). Using P. aeruginosa lipid A with different levels of acylation, we identified a 222 amino acid region in the extracellular portion of human TLR4 that is required for the differential recognition of cystic fibrosis-specific lipid A. P. aeruginosa adaptation to the human airway may, therefore, play a fundamental role in the progressive lung damage associated with cystic fibrosis.

• Authors: Robert K Ernst, Adeline M Hajjar, Jeff H Tsai, Samuel M Moskowitz, Christopher B Wilson, Samuel I Miller
• Journal: Journal of endotoxin research (J Endotoxin Res) Vol. 9 Issue 6 Pg. 395-400 ( 2003) ISSN: 0968-0519 [Print] United States
• PMID: 14733728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Lipid A
• Lipopolysaccharides
• Membrane Glycoproteins
• Receptors, Cell Surface
• TLR4 protein, human
• Toll-Like Receptor 4
• Toll-Like Receptors

Topics

• Amino Acid Sequence
• Cell Line
• Cystic Fibrosis (complications, microbiology)
• Genetic Variation
• Humans
• Kidney (cytology)
• Lipid A (chemistry, genetics, immunology)
• Lipopolysaccharides (chemistry, immunology, isolation & purification, pharmacology)
• Mass Spectrometry
• Membrane Glycoproteins (chemistry, genetics, immunology)
• Molecular Weight
• Pseudomonas aeruginosa (chemistry, genetics, growth & development, isolation & purification)
• Receptors, Cell Surface (chemistry, genetics, immunology)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Toll-Like Receptor 4
• Toll-Like Receptors
• Transfection