Single-cell phenotypic characteristics of tolerance under recurring antibiotic exposure in Escherichia coli

Non-heritable drug resistance, such as tolerance and persistence towards antibiotics, is little characterized compared to genetic resistance. Tolerance and persistence allow cells to survive application of antibiotics that are bactericidal to non-tolerant cells. Non-heritable drug resistance challenges antibiotic treatment, particularly of recurrent infections, and have implications towards heritable resistance evolution. Tolerant cells have commonly been characterized as growth arrested cells prior and during antibiotic application that quickly resume growth post-application. Here, we explore characteristic of tolerant and susceptible E. coli single bacteria cells to different levels of recurrent antibiotic exposure and quantify their occurrence. In using a high throughput single-cell microfluidic device, we find that tolerant cells reduce their growth rate by about 50%, but contrary to previous findings do not go into growth arrest or near growth arrest. The growth reduction is induce...