Ernst Robert K, Hajjar Adeline M, Tsai Jeff H, Moskowitz Samuel M, Wilson Christopher B, Miller Samuel I
Department of Medicine, HSB K-155, Box 357710, University of Washington, Seattle, WA 98195, USA.
J Endotoxin Res. 2003;9(6):395-400. doi: 10.1179/096805103225002764.
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.
脂多糖A是细菌脂多糖的促炎成分，是革兰氏阴性菌的主要表面成分。革兰氏阴性菌会根据特定的环境条件改变脂多糖A的结构，这些条件包括在宿主定植时发现的条件。机会致病菌铜绿假单胞菌在适应囊性纤维化气道的过程中会合成一种独特的含有棕榈酸酯和氨基阿拉伯糖的六酰化脂多糖A。在从非囊性纤维化相关感染中分离出的铜绿假单胞菌中观察到不同种类的脂多糖A。在此，我们报告从一名患有严重肺部疾病的囊性纤维化患者气道中分离出的铜绿假单胞菌菌株合成了一种新型的七酰化脂多糖A。囊性纤维化特异性铜绿假单胞菌脂多糖A修饰导致对宿主抗菌肽具有抗性，并增加了人 Toll 样受体 4（TLR4）的识别。使用具有不同酰化水平的铜绿假单胞菌脂多糖A，我们在人 TLR4 的细胞外部分鉴定出一个222个氨基酸的区域，该区域是对囊性纤维化特异性脂多糖A进行差异识别所必需的。因此，铜绿假单胞菌对人类气道的适应可能在与囊性纤维化相关的进行性肺损伤中起重要作用。
