RT Journal Article SR Electronic T1 Existence of log-phase Escherichia coli persisters and lasting memory of a starvation pulse JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202101076 DO 10.26508/lsa.202101076 VO 5 IS 2 A1 Svenningsen, Mikkel Skjoldan A1 Svenningsen, Sine Lo A1 Sørensen, Michael Askvad A1 Mitarai, Namiko YR 2022 UL https://www.life-science-alliance.org/content/5/2/e202101076.abstract AB The vast majority of a bacterial population is killed when treated with a lethal concentration of antibiotics. The time scale of this killing is often comparable with the bacterial generation time before the addition of antibiotics. Yet, a small subpopulation typically survives for an extended period. However, the long-term killing dynamics of bacterial cells has not been fully quantified even in well-controlled laboratory conditions. We constructed a week-long killing assay and followed the survival fraction of Escherichia coli K12 exposed to a high concentration of ciprofloxacin. We found that long-term survivors were formed during exponential growth, with some cells surviving at least 7 d. The long-term dynamics contained at least three time scales, which greatly enhances predictions of the population survival time compared with the biphasic extrapolation from the short-term behavior. Furthermore, we observed a long memory effect of a brief starvation pulse, which was dependent on the (p)ppGpp synthase relA. Specifically, 1 h of carbon starvation before antibiotics exposure increased the surviving fraction by nearly 100-fold even after 4 d of ciprofloxacin treatment.