Early Bacillus anthracis macrophage interactions:: intracellular survival and escape

Early Bacillus anthracis macrophage interactions:: intracellular survival and escape
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DOI:
10.1046/j.1462-5822.2000.00067.x
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发表时间:
2000-12-01
影响因子:
3.4
通讯作者:
Hanna, PC
Hanna, PC
中科院分区:
生物学2区
文献类型:
--
作者:
Dixon, TC;Fadl, AA;Hanna, PC

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本研究描述了炭疽杆菌感染建立阶段发生的早期细胞内事件。炭疽感染是由休眠的内生孢子进入哺乳动物宿主并被局部巨噬细胞(M phi)吞噬而引发的。在全身性炭疽病期间,晚期事件包括血液中的营养生长至非常高的滴度和炭疽外毒素复合物的合成,其引起疾病症状和死亡。实验集中在B的最初几个小时内发生的早期事件。炭疽菌的感染周期,从内生孢子萌发到吞噬细胞释放营养细胞。我们发现,新的营养杆菌逃脱的吞噬囊泡培养的M phi和复制这些细胞的细胞质内。从M phi的释放发生在内生孢子吞噬后4-6小时,时间与试验动物的炭疽感染相关。本研究的遗传分析表明,毒素质粒pXO 1是从M phi释放所必需的,而胶囊质粒pXO 2不是。位于pXO 1上的反式激活因子atxA也被发现是释放所必需的,但毒素基因本身不是必需的。这表明炭疽杆菌的M phi释放受atxA调节。推定的“逃逸”基因可能位于染色体上和/或pXO 1上。
This study describes early intracellular events occurring during the establishment phase of Bacillus anthracis infections. Anthrax infections are initiated by dormant endospores gaining access to the mammalian host and becoming engulfed by regional macrophages (M phi). During systemic anthrax, late stage events include vegetative growth in the blood to very high titres and the synthesis of the anthrax exotoxin complex, which causes disease symptoms and death. Experiments focus on the early events occurring during the first few hours of the B. anthracis infectious cycle, from endospore germination up to and including release of the vegetative cell from phagocytes. We found that newly vegetative bacilli escape from the phagocytic vesicles of cultured M phi and replicate within the cytoplasm of these cells. Release from the M phi occurs 4-6 h after endospore phagocytosis, timing that correlates with anthrax infection of test animals. Genetic analysis from this study indicates that the toxin plasmid pXO1 is required for release from the M phi, whereas the capsule plasmid pXO2 is not. The transactivator atxA, located on pXO1, is also found to be essential for release, but the toxin genes themselves are not required. This suggests that M phi release of anthrax bacilli is atxA regulated. The putative 'escape' genes may be located on the chromosome and/or on pXO1.