Identification of the lipooligosaccharide biosynthetic gene cluster from Mycobacterium marinum
Identification of the lipooligosaccharide biosynthetic gene cluster from Mycobacterium marinum
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DOI：
10.1111/j.1365-2958.2007.05603.x
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发表时间：
2007-03-01
影响因子：
3.6
通讯作者：
Liu, Jun
中科院分区：
文献类型：
--
作者：
Ren, Huiping;Dover, Lynn G.;Liu, Jun
脂寡糖是一种抗原性糖脂，存在于分枝杆菌的某些物种中，包括结核分枝杆菌的Canetti菌株。几种分枝杆菌的核心LOS结构已经确定，但丢失的生物合成途径仍不清楚。在这项研究中，我们描述了两个海洋分枝杆菌的转座子插入突变体，它们的菌落形态发生了变化。细胞壁分析表明，MRS1271突变体在合成LOS-II方面存在缺陷，而MRS1178突变体积累了介于LOS-I和-II之间的中间产物。遗传损伤定位于MM2309和MM2332两个基因。MM2309编码一种参与D-木糖合成的UDP-葡萄糖脱氢酶。预测MM2332编码一种脱羧酶。这两个基因和一个先前发现的LOSA基因定位于一个基因簇中，该基因簇可能与Lost的生物合成有关。我们的结果还表明，丢失在宿主巨噬细胞的滑动运动、生物被膜形成和感染中起着重要作用。综上所述，我们的研究首次确定了一个LOS生物合成位点。这是评估损失在分枝杆菌物种间的不同分布和了解损失在分枝杆菌毒力中的作用的重要一步。
Lipooligosaccharides (LOSs) are antigenic glycolipids that are present in some species of Mycobacterium including the Canetti strain of M. tuberculosis. The core LOS structures from several mycobacterial organisms have been established, but the biosynthetic pathways of LOSs remain unknown. In this study, we describe two transposon insertion mutants of M. marinum that exhibit altered colony morphology. Cell wall analysis reveals that the MRS1271 mutant is defective in the synthesis of LOS-II, whereas the MRS1178 mutant accumulates an intermediate between LOS-I and -II. The genetic lesions were localized to two genes, MM2309 and MM2332. MM2309 encodes a UDP-glucose dehydrogenase that is involved in the synthesis of D-xylose. MM2332 is predicted to encode a decarboxylase. These two genes and a previously identified losA gene are localized in a gene cluster likely to be involved in the biosynthesis of LOSs. Our results also show that LOSs play an important role in sliding motility, biofilm formation, and infection of host macrophages. Taken together, our studies have identified, for the first time, a LOS biosynthetic locus. This is an important step in assessing the differential distribution of LOSs among Mycobacterium species and understanding the role of LOSs in mycobacterial virulence.