TY - JOUR

T1 - Existence of log-phase Escherichia coli persisters and lasting memory of a starvation pulse

AU - Svenningsen, Mikkel Skjoldan

AU - Svenningsen, Sine Lo

AU - Sørensen, Michael Askvad

AU - Mitarai, Namiko

PY - 2022

Y1 - 2022

N2 - 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.

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.

KW - BACTERIAL PERSISTENCE

KW - TOLERANCE

KW - STRINGENT

KW - GROWTH

KW - SYSTEM

KW - GENE

KW - RNA

U2 - 10.26508/lsa.202101076

DO - 10.26508/lsa.202101076

M3 - Journal article

C2 - 34795016

VL - 5

JO - Life Science Alliance

JF - Life Science Alliance

SN - 2575-1077

IS - 2

M1 - e202101076

ER -