Phenotypic variability in the response to antibiotics
Nathalie Q.Balaban, Racah Institute for Physics, The Hebrew University, Jerusalem 91904, Israel.

When a population of genetically identical cells is exposed for several hours to an antibiotic, such as penicillin, most of the population is killed. However, when the antibiotic is removed, a small fraction of the cells survives. These cells have not genetically acquired antibiotic resistance: they re-grow a new population that is as sensitive to the antibiotic. This phenomenon, termed bacterial persistence, was first reported for Staphylococcal infections treated with penicillin and has since been observed in many bacterial species. We investigated the persistence of Escherichia coli at the level of single cells using specially conceived microfluidic devices, based on soft lithography technology. Here, we show that persistence is linked to pre-existing heterogeneity in bacterial populations. Quantitative measurements lead to a simple mathematical description of the persistence switch, revealing its characteristic time scales. The observed inherent heterogeneity of bacterial populations may play an important role in adaptation to fluctuating environments, and in the persistence of bacterial infections such as tuberculosis where a single bacterium can start an infection.