AgrD-dependent quorum sensing affects biofilm formation, invasion, virulence and global gene expression profiles in Listeria monocytogenes
AgrD-dependent quorum sensing affects biofilm formation, invasion, virulence and global gene expression profiles in Listeria monocytogenes
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DOI：
10.1111/j.1365-2958.2008.06589.x
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发表时间：
2009-03-01
影响因子：
3.6
通讯作者：
Hill, Colin
中科院分区：
文献类型：
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作者：
Riedel, Christian U.;Monk, Ian R.;Hill, Colin
通过在 agrD（假定的群体感应肽的结构基因）中创建缺失突变体，对单核细胞增生李斯特菌 Agr 肽感应系统进行了分析。 Delta agrD 突变体表现出生物膜形成显着减少，这一缺陷可以通过遗传或物理互补来恢复。观察到 Delta agrD 突变体对 Caco-2 肠上皮细胞的侵袭减少，而 THP-1 巨噬细胞的吞噬作用不受影响。另外，在Delta agrD突变体中，细胞壁中内蛋白A（InlA）的水平降低。毒力基因（hlyA、actA、plcA、prfA 和 inlA）的表达谱鉴定出一种微调调节，导致 Delta agrD 突变体毒力反应受损。体内生物发光成像显示，该突变体对小鼠的毒力也显着减弱。感染后第 3 天，野生型已发生全身性传播至肝脏和脾脏，而 Delta agrD 突变体仍局限于肝脏。微阵列分析鉴定出 126 个和 670 个基因分别在指数期和稳定期受到显着调节。这里提出的结果表明，肽传感在单增李斯特菌的生物学中发挥着重要作用，在腐生和寄生生命周期中都具有相关的表型。
The Listeria monocytogenes Agr peptide-sensing system has been analysed by creating a deletion mutant in agrD, the structural gene for the putative quorum-sensing peptide. The Delta agrD mutant displayed significantly reduced biofilm formation, a defect which could be restored by genetic or physical complementation. A reduced invasion of Caco-2 intestinal epithelial cells was observed for the Delta agrD mutant while phagocytosis by THP-1 macrophages was unaffected. Additionally, the level of internalin A (InlA) in the cell wall was decreased in the Delta agrD mutant. Expression profiling of virulence genes (hlyA, actA, plcA, prfA and inlA) identified a finely tuned regulation which resulted in an impaired virulence response in the Delta agrD mutant. The mutant is also significantly attenuated for virulence in mice, as revealed by bioluminescent in vivo imaging. On day 3 post infection, systemic dissemination to livers and spleens had occurred for the wild type, whereas the Delta agrD mutant remained localized to the liver. Microarray analysis identified 126 and 670 genes as significantly regulated in exponential and stationary phase respectively. The results presented here suggest that peptide sensing plays an important role in the biology of L. monocytogenes, with relevant phenotypes in both the saprophytic and parasitic lifecycles.