General Mechanisms Leading to Persister Formation and Awakening

Experimental evidence is accumulating for the contribution of persister cells to the recalcitrance of chronic infections and the increased development of antibiotic resistance. Target inactivity and dormancy caused by energy loss, halted DNA replication, and blocked translation contribute to persister formation. Target inactivity and dormancy cannot fully explain the complex nature of persister cells because some persisters rely on intrinsic mechanisms to repair antibiotic damage or to lower the intracellular antibiotic concentration. Depending on the persistence effector at play, persisters can have distinct physiologies that contribute to their heterogeneity within bacterial populations. In vitro evolution experiments have shown that persistence is a highly evolvable trait