Single-cell protein induction dynamics reveals a period of vulnerability to antibiotics in persister bacteria.
Phenotypic variability in populations of cells has been linked to evolutionary robustness to stressful conditions. A remarkable example of the importance of cell-to-cell variability is found in bacterial persistence, where subpopulations of dormant bacteria, termed persisters, were shown to be responsible for the persistence of the population to antibiotic treatments. Here, we use microfluidic devices to monitor the induction of fluorescent proteins under synthetic promoters and characterize the dormant state of single persister bacteria. Surprisingly, we observe that protein production does take place in supposedly dormant bacteria, over a narrow time window after the exit from stationary phase. Only thereafter does protein production stop, suggesting that differentiation into persisters fully develops over this time window and not during starvation, as previously believed. In effect, we observe that exposure of bacteria to antibiotics during this time window significantly reduces persistence. Our results point to new strategies to fight persistent bacterial infections. The quantitative measurement of single-cell induction presented in this study should shed light on the processes leading to the dormancy of subpopulations in different systems, such as in subpopulations of viable but nonculturable bacteria, or those of quiescent cancer cells.
Gefen
Orit
O
Racah Institute for Physics and Center for NanoScience and Nanotechnology, Hebrew University, Jerusalem 91904, Israel.
Gabay
Chana
C
Mumcuoglu
Michael
M
Engel
Giora
G
Balaban
Nathalie Q
NQ
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics; D018929:Cell Culture Techniques; D024881:Drug Resistance, Bacterial / Q000502:physiology*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D046210:Microfluidic Analytical Techniques; D011401:Promoter Regions, Genetic
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria