The type II O-antigenic polysaccharide moiety of Burkholderia pseudomallei lipopolysaccharide is required for serum resistance and virulence
The type II O-antigenic polysaccharide moiety of Burkholderia pseudomallei lipopolysaccharide is required for serum resistance and virulence
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DOI：
10.1046/j.1365-2958.1998.01139.x
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发表时间：
1998-12-01
影响因子：
3.6
通讯作者：
Woods, DE
中科院分区：
文献类型：
--
作者：
DeShazer, D;Brett, PJ;Woods, DE
类鼻疽病是一种由革兰氏阴性细菌病原体假马氏伯克氏菌引起的传染病，在东南亚和澳大利亚北部流行。急性败血症类鼻疽病是发病和死亡的主要原因，特别是在泰国东北部。假芽孢杆菌对正常人血清（NHS）的杀菌活性具有高度的抗性，我们发现假芽孢杆菌1026b在10-30%的NHS中繁殖。我们基于这种新表型开发了一种简单的筛选血清敏感突变体的方法。筛选了大约1200个Tn5-OT182突变体，鉴定出3个血清敏感突变体。脂多糖的II型o -抗原多糖（O-PS）部分在血清敏感突变体中不存在。在三种类鼻窦炎动物模型中，具有代表性的血清敏感突变体SRM117被补体替代途径杀死，其毒性低于1026b。血清敏感突变体的Tn5-OT182整合在假瘤芽孢杆菌染色体上物理连接，进一步的遗传分析显示，该基因座包含15个基因，是II型O-PS产生所需的基因簇。这些基因编码的蛋白质与参与细菌多糖生物合成的蛋白质相似。本研究结果表明，II型O-PS对假芽孢杆菌的血清耐药性和毒力至关重要。
Melioidosis, an infection caused by the Gram-negative bacterial pathogen Burkholderia pseudomallei, is endemic in south-east Asia and northern Australia, Acute septicaemic melioidosis is a major cause of morbidity and mortality, especially in north-east Thailand. B. pseudomallei is highly resistant to the bactericidal activity of normal human serum (NHS), and we have found that B. pseudomallei 1026b multiplies in 10-30% NHS. We developed a simple screen for the identification of serum-sensitive mutants based on this novel phenotype. Approximately 1200 Tn5-OT182 mutants were screened, and three serum-sensitive mutants were identified. The type II O-antigenic polysaccharide (O-PS) moiety of lipopolysaccharide was not present in the serum-sensitive mutants. A representative serum-sensitive mutant, SRM117, was killed by the alternative pathway of complement and was less virulent than 1026b in three animal models of melioidosis. The Tn5-OT182 integrations in the serum-sensitive mutants were physically linked on the B. pseudomallei chromosome, and further genetic analysis of this locus revealed a cluster of 15 genes required for type II O-PS production. The proteins encoded by these genes were similar to proteins involved in bacterial polysaccharide biosynthesis. The results presented here demonstrate that type II O-PS is essential for B. pseudomallei serum resistance and virulence.