The temporal expression profile of Mycobacterium tuberculosis infection in mice
The temporal expression profile of Mycobacterium tuberculosis infection in mice
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DOI：
10.1073/pnas.0306023101
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发表时间：
2004-03-30
影响因子：
11.1
通讯作者：
Johnston, SA
中科院分区：
文献类型：
--
作者：
Talaat, AM;Lyons, R;Johnston, SA
结核分枝杆菌感染引起的结核病每年的死亡人数约为200万。了解结核病不同阶段宿主-病原体相互作用的性质对于开发化疗和疫苗的新策略至关重要。为此，我们采用微阵列技术来分析M。结核病在小鼠感染期间。该方案提供了在免疫活性（BALB/c）和严重联合免疫缺陷（SCID）宿主的早期结核病过程中表达的基因的转录谱，并与培养基中的生长进行了比较。微阵列分析揭示了随时间推移仅在BALB/c、SCID小鼠或培养基的肺中改变其转录水平的基因簇。我们确定了一组基因（n = 67）仅在感染后21天在BALB/c中激活，而在SCID小鼠中未激活，这是结核病进展的关键点。肺激活基因的一个子集先前被确定为在巨噬细胞系中分枝杆菌存活期间诱导的。另一组在体内表达的基因也可能定义一个以前未报道的基因组岛。此外，我们的分析表明，在SCID和肉汤中生长期间分枝杆菌转录机制之间的相似性，这质疑使用SCID模型评估分枝杆菌毒力的有效性。提出的体内表达谱技术应该适用于任何感染的微生物模型。
Infection with Mycobacterium tuberculosis causes the illness tuberculosis with an annual mortality of approximate to2 million. Understanding the nature of the host-pathogen interactions at different stages of tuberculosis is central to new strategies for developing chemotherapies and vaccines. Toward this end, we adapted microarray technology to analyze the change in gene expression profiles of M. tuberculosis during infection in mice. This protocol provides the transcription profile of genes expressed during the course of early tuberculosis in immune-competent (BALB/c) and severe combined immune-deficient (SCID) hosts in comparison with growth in medium. The microarray analysis revealed clusters of genes that changed their transcription levels exclusively in the lungs of BALB/c, SCID mice, or medium over time. We identified a set of genes (n = 67) activated only in BALB/c and not in SCID mice at 21 days after infection, a key point in the progression of tuberculosis. A subset of the lung-activated genes was previously identified as induced during mycobacterial survival in a macrophage cell line. Another group of in vivo-expressed genes may also define a previously unreported genomic island. In addition, our analysis suggests the similarity between mycobacterial transcriptional machinery during growth in SCID and in broth, which questions the validity of using the SCID model for assessing mycobacterial virulence. The in vivo expression-profiling technology presented should be applicable to any microbial model of infection.