IDENTIFICATION OF A LEGIONELLA-PNEUMOPHILA LOCUS REQUIRED FOR INTRACELLULAR MULTIPLICATION IN HUMAN MACROPHAGES
IDENTIFICATION OF A LEGIONELLA-PNEUMOPHILA LOCUS REQUIRED FOR INTRACELLULAR MULTIPLICATION IN HUMAN MACROPHAGES
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DOI：
10.1073/pnas.89.20.9607
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发表时间：
1992-10-15
影响因子：
11.1
通讯作者：
SHUMAN, HA
中科院分区：
文献类型：
--
作者：
MARRA, A;BLANDER, SJ;SHUMAN, HA
军团病细菌，嗜肺军团菌，是一种兼性细胞内寄生虫。它与吞噬细胞的相互作用与其他几种细胞内寄生虫有共同的特点。嗜肺乳杆菌细胞内增殖的关键方面是逃避溶酶体宿主细胞防御和营养适宜环境的存在。吞噬作用后，野生型嗜肺乳杆菌在不与次级溶酶体融合的特殊吞噬体内繁殖。失去在吞噬细胞内生长能力的突变体在动物中不再引起疾病，这表明细胞内繁殖的能力对发病机制很重要。其中一个突变体，25D，已被证明在抑制吞噬体-溶酶体融合方面存在缺陷。这种吞噬溶酶体环境不利于军团菌的生长。我们报道了嗜肺杆菌基因组（icm，细胞内增殖）的一个区域的分离，该区域恢复了25D在人巨噬细胞中的增殖能力。补充突变体也重新获得干扰吞噬体-溶酶体融合的能力，并在豚鼠中引起致死性肺炎。
The legionnaires' disease bacterium, Legionella pneumophila, is a facultative intracellular parasite. Its interaction with phagocytes has characteristics in common with several other intracellular parasites. Critical aspects of L. pneumophila intracellular multiplication are evasion of lysosomal host cell defenses and the presence of a nutritionally appropriate environment. Following phagocytosis, wild-type L. pneumophila multiply within a specialized phagosome which does not fuse with secondary lysosomes. Mutants which have lost the ability to grow within phagocytes no longer cause disease in animals, indicating that the capacity to multiply intracellularly is important for pathogenesis. One such mutant, 25D, has been shown to be defective in inhibiting phagosome-lysosome fusion. This phagolysosomal environment is not conducive to Legionella growth. We report the isolation of a region of the L. pneumophila genome (icm, intracellular multiplication) which restores the capacity of 25D to multiply in human macrophages. The complemented mutants also regain the capacity to interfere with phagosome-lysosome fusion and to cause lethal pneumonia in guinea pigs.