Intracellular gene expression profile of Listeria monocytogenes
Intracellular gene expression profile of Listeria monocytogenes
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DOI：
10.1128/iai.74.2.1323-1338.2006
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发表时间：
2006-02-01
影响因子：
3.1
通讯作者：
Hain, T
中科院分区：
文献类型：
--
作者：
Chatterjee, SS;Hossain, H;Hain, T
单核细胞增多性李斯特菌是一种革兰氏阳性的食源性微生物，可引起侵袭性感染，总体死亡率较高。单核细胞增多性乳杆菌是为数不多的能够诱导摄取进入宿主细胞并随后通过破坏液泡膜进入宿主细胞胞浆的微生物之一。我们用单核细胞增生性李斯特菌EGD-e株感染小鼠巨噬细胞系P388D1，通过全基因组芯片和突变分析检测了单核细胞增多性李斯特菌在宿主细胞空泡和胞浆环境中的基因表达谱。我们发现，大约17%的总基因组被动员起来，以适应细胞内的生长。细胞内表达的基因表现出典型的细菌内葡萄糖限制的反应，中央代谢中编码酶的mRNA数量减少，参与替代碳源利用途径及其调控的基因暂时诱导。适应性细胞内基因表达涉及与毒力、一般胁迫反应、细胞分裂和细胞壁结构变化相关的基因，其中包括许多未知功能的基因。共有41个基因是物种特异性的，在非致病性无毒李斯特菌Clip 11262株的基因组中缺失。我们还检测到了25个菌株特有的基因，即先前测序的单核细胞增多性李斯特菌F2365血清型4b株基因组中缺失的基因，这表明单核细胞增多性李斯特菌在宿主细胞内存活所需的基因库中存在异质性。总体而言，我们的研究为单核细胞增多性李斯特菌逃避宿主细胞反应的细胞内生存策略和措施提供了重要的见解。
Listeria monocytogenes is a gram-positive, food-borne microorganism responsible for invasive infections with a high overall mortality. L. monocytogenes is among the very few microorganisms that can induce uptake into the host cell and subsequently enter the host cell cytosol by breaching the vacuolar membrane. We infected the murine macrophage cell line P388D1 with L. monocytogenes strain EGD-e and examined the gene expression profile of L. monocytogenes inside the vacuolar and cytosolic environments of the host cell by using whole-genome microarray and mutant analyses. We found that similar to 17% of the total genome was mobilized to enable adaptation for intracellular growth. Intracellularly expressed genes showed responses typical of glucose limitation within bacteria, with a decrease in the amount of mRNA encoding enzymes in the central metabolism and a temporal induction of genes involved in alternative-carbon-source utilization pathways and their regulation. Adaptive intracellular gene expression involved genes that are associated with virulence, the general stress response, cell division, and changes in cell wall structure and included many genes with unknown functions. A total of 41 genes were species specific, being absent from the genome of the nonpathogenic Listeria innocua CLIP 11262 strain. We also detected 25 genes that were strain specific, i.e., absent from the genome of the previously sequenced L. monocytogenes F2365 serotype 4b strain, suggesting heterogeneity in the gene pool required for intracellular survival of L. monocytogenes in host cells. Overall, our study provides crucial insights into the strategy of intracellular survival and measures taken by L. monocytogenes to escape the host cell responses.