Persister bacteria

Stress responses, whether specific or general, usually involve the activation of gene expression in reaction to a stress signal. For strong and fast-acting stresses (e.g., extensive antibiotic exposure), the response may be too slow to be effective. Nevertheless, an alternative strategy makes the survival of bacterial populations possible under antibiotic stress: the generation of subpopulations that, previous to exposure to antibiotics, are preadapted to stress by means of a reduced growth rate that enables them to persist under antibiotics. The phenomenon of bacterial persistence was noticed as early as 1944 when Bigger observed that bacterial cultures were rarely sterilized by antibiotics (Bigger, 1944). He realized that bacteria that managed to survive an antibiotic treatment of several hours, termed persisters, were not resistant mutants. When regrown, the survivors generated a bacterial population as sensitive to the antibiotic as the original population-which is not the case in resistance that is genetically acquired and passed on to subsequent generations. For many years, persistence was overlooked mainly because, in most bacterial infections, the small fraction of persisters is eventually eliminated by the immune system. However, it has become increasingly obvious that persistence is a major problem in diseases where the immune system proves ineffective and even a small number of surviving bacteria can restart an infection. Furthermore, persisters that remain viable despite extensive antibiotic treatments may provide the fertile ground required for the emergence of antibiotic resistance. Understanding the mechanisms leading to persistence should have wide implications in the fight against bacterial infections and in the unveiling of the different ways in which bacteria deal with stress. Here we focus on persistence in Escherichia coli because recent genetic analysis and novel tools for studying persistence in single cells have resulted in new data, but persistence is a ubiquitous phenomenon observed in many different bacterial species. Persistence may be a bet-hedging strategy for survival in fluctuating stressful environments. Still, the identification and characterization of underlying mechanisms responsible for persistence await future studies.