Intracellular biology and virulence determinants of Francisella tularensis revealed by transcriptional profiling inside macrophages.
Intracellular biology and virulence determinants of Francisella tularensis revealed by transcriptional profiling inside macrophages.
复制标题
DOI：
10.1111/j.1462-5822.2009.01316.x
复制
发表时间：
2009-07
影响因子：
3.4
通讯作者：
Celli J
中科院分区：
文献类型：
--
作者：
Wehrly TD;Chong A;Virtaneva K;Sturdevant DE;Child R;Edwards JA;Brouwer D;Nair V;Fischer ER;Wicke L;Curda AJ;Kupko JJ 3rd;Martens C;Crane DD;Bosio CM;Porcella SF;Celli J
高度传染性的土拉弗朗西斯菌是一种兼性细胞内病原体，其毒力需要在宿主细胞（包括巨噬细胞）内增殖。在这里，我们对高毒力的 F. tularensis 亚种进行了全局转录分析。 tularensis Schu S4 菌株在原代小鼠巨噬细胞内的细胞内周期中，以表征其细胞内生物学并根据其细胞内表达谱鉴定致病决定因素。吞噬细菌快速响应其细胞内环境，随后改变其转录谱。揭示了与细菌特定细胞内区域相关的差异基因表达谱。一般和氧化应激反应基因的上调是早期吞噬体和晚期内体阶段的标志，而运输和代谢基因的诱导是胞质复制阶段的特征。细胞内增殖所需的弗朗西斯菌致病岛（FPI）基因的表达在细胞内周期期间增加。同样，编码假定的、分泌的、外膜蛋白或转录调节因子的 27 个染色体位点被鉴定为上调。其中，FTT0383、FTT0369c 或 FTT1676 的缺失消除了 Schu S4 在细胞内存活或增殖并导致小鼠死亡的能力，因此从其细胞内表达谱中鉴定了弗朗西斯菌毒力的新决定因素。
The highly infectious bacterium Francisella tularensis is a facultative intracellular pathogen, whose virulence requires proliferation inside host cells, including macrophages. Here we have performed a global transcriptional profiling of the highly virulent F. tularensis subsp. tularensis Schu S4 strain during its intracellular cycle within primary murine macrophages, to characterize its intracellular biology and identify pathogenic determinants based on their intracellular expression profiles. Phagocytosed bacteria rapidly responded to their intracellular environment and subsequently altered their transcriptional profile. Differential gene expression profiles were revealed that correlated with specific intracellular locale of the bacteria. Upregulation of general and oxidative stress response genes was a hallmark of the early phagosomal and late endosomal stages, while induction of transport and metabolic genes characterized the cytosolic replication stage. Expression of the Francisella Pathogenicity Island (FPI) genes, which are required for intracellular proliferation, increased during the intracellular cycle. Similarly, 27 chromosomal loci encoding putative hypothetical, secreted, outer membrane proteins or transcriptional regulators were identified as upregulated. Among these, deletion of FTT0383, FTT0369c or FTT1676 abolished the ability of Schu S4 to survive or proliferate intracellularly and cause lethality in mice, therefore identifying novel determinants of Francisella virulence from their intracellular expression profile.
登录
查看更多内容
影响因子：
3.1
作者：
Chatterjee, SS;Hossain, H;Hain, T
通讯作者：
Hain, T
影响因子：
3.1
作者：
Golovliov, I;Baranov, V;Sjöstedt, A
通讯作者：
Sjöstedt, A
影响因子：
3.1
作者：
Fontan, Patricia;Aris, Virginie;Smith, Issar
通讯作者：
Smith, Issar
影响因子：
30.8
作者：
Larsson, P;Oyston, PCF;Titball, RW
通讯作者：
Titball, RW
DOI：
10.1073/pnas.0601838103
发表时间：
2006-09-26
影响因子：
11.1
作者：
Checroun, Claire;Wehrly, Tara D.;Celli, Jean
通讯作者：
Celli, Jean