Hagedorn Monica, Soldati Thierry
Départment de Biochimie, Faculté des Sciences, Université de Genève, Sciences II, 30 quai Ernest Ansermet, CH-1211-Genève-4, Switzerland.
Cell Microbiol. 2007 Nov;9(11):2716-33. doi: 10.1111/j.1462-5822.2007.00993.x. Epub 2007 Jun 24.
Mycobacterium marinum, a close relative of Mycobacterium tuberculosis, provides a useful model to study the pathogenesis of tuberculosis in genetically tractable model organisms. Using the amoeba Dictyostelium discoideum as a host, we show that expression of the M. marinum protein MAG24-1 is crucial to interfere with phagosome maturation. We find that two host proteins - the flotillin homologue vacuolin and p80, a predicted copper transporter - accumulate at the vacuole during pathogen replication until it finally ruptures and the bacteria are released into the host cytosol. Flotillin-1 accumulation at the replication niche and its rupture were also observed in human peripheral blood monocytes. By infecting various Dictyostelium mutants, we show that the absence of one of the two Dictyostelium vacuolin isoforms renders the host more immune to M. marinum. Conversely, the absence of the small GTPase RacH renders the host more susceptible to M. marinum proliferation but inhibits its cell-to-cell spreading.
海分枝杆菌是结核分枝杆菌的近亲，它为在基因易处理的模式生物中研究结核病的发病机制提供了一个有用的模型。利用变形虫盘基网柄菌作为宿主，我们发现海分枝杆菌蛋白MAG24-1的表达对于干扰吞噬体成熟至关重要。我们发现两种宿主蛋白——小窝蛋白同源物液泡蛋白和预测的铜转运蛋白p80——在病原体复制过程中在液泡处积累，直到液泡最终破裂，细菌释放到宿主细胞质中。在人类外周血单核细胞中也观察到小窝蛋白-1在复制位点的积累及其破裂。通过感染各种盘基网柄菌突变体，我们发现两种盘基网柄菌液泡蛋白亚型之一的缺失使宿主对海分枝杆菌更具免疫力。相反，小GTP酶RacH的缺失使宿主更容易受到海分枝杆菌增殖的影响，但抑制其细胞间传播。
