A mycobacterial gene involved in synthesis of an outer cell envelope lipid is a key factor in prevention of phagosome maturation
A mycobacterial gene involved in synthesis of an outer cell envelope lipid is a key factor in prevention of phagosome maturation
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DOI：
10.1128/iai.00997-06
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发表时间：
2007-02-01
影响因子：
3.1
通讯作者：
Plum, Georg
中科院分区：
文献类型：
--
作者：
Robinson, Nirmal;Wolke, Martina;Plum, Georg
毒力分枝杆菌会导致吞噬体成熟停滞，作为其在宿主中生存策略的一部分。这一过程是通过多种毒力因子介导的，其分子性质仍然难以捉摸。使用海分枝杆菌作为模型，我们进行了全基因组筛选，以确定抑制吞噬体成熟的能力受损的突变体，并且我们成功地分离出了一组不能占据哺乳动物巨噬细胞中早期内体样吞噬体区室的突变体。根据基因家族对多个突变进行分类和排序表明，调节细胞包膜的基因是阻止吞噬体成熟的主要因素。特别是，我们鉴定了一个新基因 pmiA，它能够影响细胞包膜脂质的构成，从而导致吞噬体成熟受阻。 pmiA突变体不能抵抗吞噬体成熟，并且在小鼠体内严重减毒。用野生型基因补充突变体可将小鼠中减弱的毒力恢复至野生型水平。
Virulent mycobacteria cause arrest of phagosome maturation as a part of their survival strategy in hosts. This process is mediated through multiple virulence factors, whose molecular nature remains elusive. Using Mycobacterium marinum as a model, we performed a genome-wide screen to identify mutants whose ability to inhibit phagosome maturation was impaired, and we succeeded in isolating a comprehensive set of mutants that were not able to occupy an early endosome-like phagosomal compartment in mammalian macrophages. Categorizing and ordering the multiple mutations according to their gene families demonstrated that the genes modulating the cell envelope are the principal factors in arresting phagosome maturation. In particular, we identified a novel gene, pmiA, which is capable of influencing the constitution of the cell envelope lipids, thereby leading to the phagosome maturation block. The pmiA mutant was not able to resist phagosome maturation and was severely attenuated in mice. Complementing the mutant with the wild-type gene restored the attenuated virulence to wild-type levels in mice.