Persister Cells Resuscitate Using Membrane Sensors that Activate Chemotaxis, Lower cAMP Levels, and Revive Ribosomes
Persister Cells Resuscitate Using Membrane Sensors that Activate Chemotaxis, Lower cAMP Levels, and Revive Ribosomes
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DOI：
10.1016/j.isci.2019.100792
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发表时间：
2018-12
期刊：
影响因子：
5.8
通讯作者：
Ryota Yamasaki;Sooyeon Song;M. Benedik;T. Wood
中科院分区：
文献类型：
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作者：
Ryota Yamasaki;Sooyeon Song;M. Benedik;T. Wood
持久性，即耐受压力的状态，可以说是最重要的表型，因为几乎所有的细胞都会经历营养压力，这会导致亚群休眠。然而，持续性细胞如何唤醒以重建感染尚不清楚。在这里，使用单细胞观察，我们确定大肠杆菌persister细胞复苏主要是当特定的碳源，而不是自发的。此外，我们还发现持续细胞的唤醒机制是通过趋化性和磷酸转移酶膜蛋白来感受营养物质。此外，营养转运通过酶IIA降低第二信使cAMP的水平; cAMP水平的这种降低导致核糖体复苏和拯救。复苏的细胞也立即开始对营养物质的趋化性，尽管鞭毛运动不是唤醒所必需的。因此，持续细胞通过经由膜受体感知营养物而唤醒，所述膜受体经由次级信使cAMP将信号传递到核糖体，并且持续细胞唤醒并利用趋化性来获取营养物。
Persistence, the stress-tolerant state, is arguably the most vital phenotype since nearly all cells experience nutrient stress, which causes a sub-population to become dormant. However, how persister cells wake to reconstitute infections is not understood well. Here, using single-cell observations, we determined thatEscherichia colipersister cells resuscitate primarily when presented with specific carbon sources, rather than spontaneously. In addition, we found that the mechanism of persister cell waking is through sensing nutrients by chemotaxis and phosphotransferase membrane proteins. Furthermore, nutrient transport reduces the level of secondary messenger cAMP through enzyme IIA; this reduction in cAMP levels leads to ribosome resuscitation and rescue. Resuscitating cells also immediately commence chemotaxis toward nutrients, although flagellar motion is not required for waking. Hence, persister cells wake by perceiving nutrients via membrane receptors that relay the signal to ribosomes via the secondary messenger cAMP, and persisters wake and utilize chemotaxis to acquire nutrients.