Virulence strategies for infecting phagocytes deduced from the in vivo transcriptional program of Legionella pneumophila
Virulence strategies for infecting phagocytes deduced from the in vivo transcriptional program of Legionella pneumophila
复制标题
DOI：
10.1111/j.1462-5822.2006.00703.x
复制
发表时间：
2006-08-01
影响因子：
3.4
通讯作者：
Buchrieser, Carmen
中科院分区：
文献类型：
--
作者：
Bruggemann, Holger;Hagman, Arne;Buchrieser, Carmen
对宿主环境的适应和宿主细胞功能的利用对于胞内病原体的成功至关重要。在这里，洞察这些毒力机制首次从人类病原体嗜肺军团菌在其天然宿主，卡氏阿米巴感染的转录程序。生活史的双相性。嗜肺菌的基因表达从复制期到传递期的重大转变反映了这一点，涉及基因组中预测的近一半基因。然而，三种不同的L.嗜肺军团菌菌株显示出相似的体内基因表达模式，表明尽管军团菌基因组具有可塑性，但其生命周期受共同的调节机制支配。在复制阶段，除了有氧代谢和氨基酸催化剂的成分，Entner-Doudoroff途径，用于糖和/或葡萄糖酸同化的NADPH产生机制，首次表明细胞内L.嗜肺菌还可以将碳水化合物作为营养物而不仅仅是蛋白质来寄生。鉴定出的基因仅在体内上调而在体外不上调，这可能解释了体内生长的L.嗜肺菌在生命周期的后期，L。嗜肺菌上调被预测促进新宿主细胞的传递和操纵的基因，从而引发其进行下一次攻击。这些包括Dot/Icm分泌系统的底物、先前与侵袭和毒力相关的其它因子、运动性和IV型菌毛机制，以及迄今为止未表征的> 90种蛋白质。对fliA（sigma（28））缺失突变体的分析鉴定了与鞭毛调节子共调节的基因，包括GGDEF/EAL调节子和促进宿主细胞进入和存活的因子。
Adaptation to the host environment and exploitation of host cell functions are critical to the success of intracellular pathogens. Here, insight to these virulence mechanisms was obtained for the first time from the transcriptional program of the human pathogen Legionella pneumophila during infection of its natural host, Acanthamoeba castellanii. The biphasic life cycle of L. pneumophila was reflected by a major shift in gene expression from replicative to transmissive phase, concerning nearly half of the genes predicted in the genome. However, three different L. pneumophila strains showed similar in vivo gene expression patterns, indicating that common regulatory mechanisms govern the Legionella life cycle, despite the plasticity of its genome. During the replicative phase, in addition to components of aerobic metabolism and amino acid catabolism, the Entner-Doudoroff pathway, a NADPH producing mechanism used for sugar and/or gluconate assimilation, was expressed, suggesting for the first time that intracellular L. pneumophila may also scavenge host carbohydrates as nutrients and not only proteins. Identification of genes only upregulated in vivo but not in vitro, may explain higher virulence of in vivo grown L. pneumophila. Late in the life cycle, L. pneumophila upregulates genes predicted to promote transmission and manipulation of a new host cell, therewith priming it for the next attack. These including substrates of the Dot/Icm secretion system, other factors associated previously with invasion and virulence, the motility and the type IV pilus machineries, and > 90 proteins not characterized so far. Analysis of a fliA (sigma(28)) deletion mutant identified genes coregulated with the flagellar regulon, including GGDEF/EAL regulators and factors that promote host cell entry and survival.