Secondary acylation of Klebsiella pneumoniae lipopolysaccharide contributes to sensitivity to antibacterial peptides
Secondary acylation of Klebsiella pneumoniae lipopolysaccharide contributes to sensitivity to antibacterial peptides
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DOI：
10.1074/jbc.m701454200
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发表时间：
2007-05-25
影响因子：
4.8
通讯作者：
Strugnell, Richard A.
中科院分区：
文献类型：
--
作者：
Clements, Abigail;Tull, Dedreia;Strugnell, Richard A.
肺炎克雷伯菌是院内革兰氏阴性败血症的重要原因。脂多糖(LPS)被认为是这种被包裹的细菌的主要毒力决定因素，大多数脂多糖A锚的突变对细菌是有条件的致命的。我们利用LpxM突变(msbB/waan)研究了内毒素酰化在肺炎克雷伯菌发病机制中的作用。lpxM编码未成熟的脂蛋白A分子的晚期次级酰化。在小鼠肺炎模型中，肺炎克雷伯菌B5055(K2：O1)lpxM突变株被发现在肺部生长减弱，导致该细菌的致死率降低。与非包膜突变体B5055 nm不同，B5055 Delta lpxM对吞噬或补体介导的裂解的敏感性与B5055相似。在体外，B5055 Delta lpxM显示外膜通透性增加，对某些抗菌肽的敏感性增加，提示体内衰减可能部分是由于对BALB/c小鼠肺内存在的抗菌肽的敏感性所致。这些数据支持这样一种观点，即脂多糖的酰化作用在为革兰氏阴性菌提供一些对结构性和天然防御的抵抗力方面起着重要作用，特别是洗涤剂(如胆汁)和阳离子防御素的抗菌特性。
Klebsiella pneumoniae is an important cause of nosocomial Gram-negative sepsis. Lipopolysaccharide (LPS) is considered to be a major virulence determinant of this encapsulated bacterium and most mutations to the lipid A anchor of LPS are conditionally lethal to the bacterium. We studied the role of LPS acylation in K. pneumoniae disease pathogenesis by using a mutation of lpxM (msbB/waaN), which encodes the enzyme responsible for late secondary acylation of immature lipid A molecules. A K. pneumoniae B5055 (K2:O1) lpxM mutant was found to be attenuated for growth in the lungs in a mouse pneumonia model leading to reduced lethality of the bacterium. B5055 Delta lpxM exhibited similar sensitivity to phagocytosis or complement-mediated lysis than B5055, unlike the non-encapsulated mutant B5055nm. In vitro, B5055 Delta lpxM showed increased permeability of the outer membrane and an increased susceptibility to certain antibacterial peptides suggesting that in vivo attenuation may be due in part to sensitivity to antibacterial peptides present in the lungs of BALB/c mice. These data support the view that lipopolysaccharide acylation plays a important role in providing Gram-negative bacteria some resistance to structural and innate defenses and especially the antibacterial properties of detergents (e. g. bile) and cationic defensins.