Identification of two Mycobacterium marinum loci that affect interactions with macrophages
Identification of two Mycobacterium marinum loci that affect interactions with macrophages
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DOI：
10.1128/iai.72.12.6902-6913.2004
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发表时间：
2004-12-01
影响因子：
3.1
通讯作者：
Cirillo, JD
中科院分区：
文献类型：
--
作者：
El-Etr, SH;Subbian, S;Cirillo, JD
海洋分枝杆菌与人类结核病的病因--结核分枝杆菌关系密切。海洋分枝杆菌已成为研究引起人类结核病的分子机制的重要模式系统。通过对致病性和非致病性分枝杆菌差异的分子遗传学分析，我们确定了影响海洋分枝杆菌感染巨噬细胞能力的两个基因座，分别为Mel(1)和Mel(2)。对这些基因座的11个推测基因的计算机分析表明，MEL(1)编码分泌蛋白，包括一个推定的膜蛋白和两个推定的谷氨酰胺转氨酶，而MEL(2)参与次生代谢或脂肪酸的生物合成。有趣的是，Mel(2)是海洋分枝杆菌和结核分枝杆菌复合体所独有的，在任何其他已测序的分枝杆菌物种中都不存在。通过等位基因交换构建的带有MEL(1)和MEL(2)突变的海洋分枝杆菌突变株，在感染小鼠和鱼类巨噬细胞系的能力方面存在缺陷。这些数据表明，Mel(1)和Mel(2)中的基因对于海洋分枝杆菌感染宿主细胞的能力是重要的。
Mycobacterium marinum is closely related to Mycobacterium tuberculosis, the cause of tuberculosis in humans. M. marinum has become an important model system for the study of the molecular mechanisms involved in causing tuberculosis in humans. Through molecular genetic analysis of the differences between pathogenic and nonpathogenic mycobacteria, we identified two loci that affect the ability of M. marinum to infect macrophages, designated mel(1) and mel(2). In silico analyses of the 11 putative genes in these loci suggest that mel(1) encodes secreted proteins that include a putative membrane protein and two putative transglutaminases, whereas mel(2) is involved in secondary metabolism or biosynthesis of fatty acids. Interestingly, mel(2) is unique to M. marinum and the M. tuberculosis complex and not present in any other sequenced mycobacterial species. M. marinum mutants with mutations in mel(1) and mel(2), constructed by allelic exchange, are defective in the ability to infect both murine and fish macrophage cell lines. These data suggest that the genes in mel(1) and mel(2) are important for the ability of M. marinum to infect host cells.