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首页> 外文期刊>Infection and immunity >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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A Mycobacterial Gene Involved in Synthesis of an Outer Cell Envelope Lipid Is a Key Factor in Prevention of Phagosome Maturation

机译：参与外细胞包膜脂质合成的分枝杆菌基因是预防卵泡成熟的关键因素

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摘要

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.
机译：毒性分枝杆菌会导致吞噬体成熟停止，这是它们在宿主中生存策略的一部分。这个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 Marinbacterium marinum 作为模型，我们进行了全基因组筛选，以鉴定其抑制吞噬体成熟能力受损的突变体，并成功分离出了一组不能占据噬菌体成熟能力的突变体。哺乳动物巨噬细胞中的早期内涵体样吞噬区室。根据其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 ，该基因能够影响细胞膜脂质的组成，从而导致吞噬体成熟。 pmiA 突变体不能抵抗吞噬体的成熟，并在小鼠中严重减毒。用野生型基因对突变体进行补充，将减毒的毒力恢复到小鼠的野生型水平。

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