Bacterial Dormancy and Persister Cells: Molecular Insights and Clinical Implications for Antimicrobial Resistance – A Narrative Review

Bacterial persisters are a tiny group of bacterial cells that manage to survive antibiotic exposure without becoming genetically resistant. These cells slip into a temporary resting state that protects them from drugs and lets the infection come back later. Their formation is influenced by many stress factors such as antibiotics, the host’s immune molecules like reactive oxygen and nitrogen species, a lack of nutrients, and the slow-growth conditions found in biofilms. Inside the cell, several survival systems work together including the stringent response, toxin-antitoxin activity, ribosome hibernation, protein and DNA repair mechanisms, and changes in energy balance to keep the bacteria dormant but alive. Studies using single-cell tools show that not all persisters behave the same; some wake up quickly when the stress is gone, while others take much longer. The return to activity mainly depends on the recovery of energy, protein quality, and translation processes, all of which are shaped by signals from the surrounding environment and host tissues. Understanding how these cells go to sleep and wake again has led to new treatment ideas such as forcing them to wake before applying antibiotics (“wake-and-kill”) or targeting them while they are still inactive (“kill-in-sleep”). Even with these advances, it remains difficult to clearly define persisters or to turn lab findings into reliable clinical treatments.