Cryptic prophages are not genomic junk but instead enable cells to combat myriad stresses as an active stress response. How these phage fossils affect persister cell resuscitation has, however, not been explored. Persister cells form as a result of stresses such as starvation, antibiotics and oxidative conditions, and resuscitation of these persister cells likely causes recurring infections such as those associated with tuberculosis, cystic fibrosis and Lyme disease. Deletion of each of the nine Escherichia coli cryptic prophages has no effect on persister cell formation. Strikingly, elimination of each cryptic prophage results in an increase in persister cell resuscitation with a dramatic increase in resuscitation upon deleting all nine prophages. This increased resuscitation includes eliminating the need for a carbon source and is due to activation of the phosphate import system resulting from inactivating the transcriptional regulator AlpA of the CP4-57 cryptic prophage. Deletion of alpA increases persister resuscitation, and AlpA represses phosphate regulator PhoR. Both phosphate regulators PhoP and PhoB stimulate resuscitation. This suggests a novel cellular stress mechanism controlled by cryptic prophages: regulation of phosphate uptake which controls the exit of the cell from dormancy and prevents premature resuscitation in the absence of nutrients.

中文翻译：

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大肠杆菌隐匿性前噬菌体感知营养物质以影响持久细胞复苏

隐蔽的前噬菌体不是基因组垃圾，而是使细胞能够作为一种积极的应激反应来对抗无数的压力。然而，尚未探索这些噬菌体化石如何影响持久细胞复苏。持久性细胞是饥饿、抗生素和氧化条件等压力的结果，这些持久性细胞的复苏可能会导致反复感染，例如与结核病、囊性纤维化和莱姆病相关的感染。删除九个大肠杆菌中的每一个隐性前噬菌体对持久细胞的形成没有影响。引人注目的是，消除每种神秘的前噬菌体会导致持久细胞复苏的增加，同时在删除所有九种前噬菌体后复苏会显着增加。这种增加的复苏包括消除对碳源的需要，并且是由于磷酸盐输入系统的激活导致了 CP4-57 隐性前噬菌体的转录调节因子 AlpA 的失活。删除alpA增加持久复苏，AlpA 抑制磷酸盐调节剂 PhoR。磷酸盐调节剂 PhoP 和 PhoB 都能刺激复苏。这表明了一种由神秘的前噬菌体控制的新的细胞应激机制：调节磷酸盐的吸收，从而控制细胞从休眠状态中退出，并防止在没有营养的情况下过早复苏。