Bacterial persisters are a stochastically formed subpopulation of low-energy cells

• Published in: PLoS biology Vol. 19; no. 4; p. e3001194
• Main Authors: Manuse, Sylvie, Shan, Yue, Canas-Duarte, Silvia J., Bakshi, Somenath, Sun, Wei-Sheng, Mori, Hirotada, Paulsson, Johan, Lewis, Kim
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.04.2021; Public Library of Science (PLoS)
• Subjects: Abbreviations; Ampicillin; Analysis; Anti-Bacterial Agents - pharmacology; Antibiotics; Antitoxins; ATP; Bacteria - drug effects; Bacteria - genetics; Bacteria - growth & development; Bacteria - metabolism; Bacterial Physiological Phenomena - drug effects; Bacteriology; Biology and Life Sciences; Carbon; Cellular Biology; Citric Acid Cycle - drug effects; Colonies; Computer and Information Sciences; Dehydrogenases; Drug Resistance, Multiple, Bacterial - drug effects; E coli; Energy; Energy Metabolism - drug effects; Energy Metabolism - physiology; Engineering and Technology; Enzymes; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - growth & development; Escherichia coli - metabolism; Flow cytometry; Fluorescence; Isocitrate dehydrogenase; Kinases; Krebs cycle; Life Sciences; Medicine and Health Sciences; Methods; Microbial Sensitivity Tests; Microbial Viability - drug effects; Microbiology and Parasitology; Microfluidics; Organisms, Genetically Modified; Physical Sciences; Physiological aspects; Population; Properties; Protein transport; Research and Analysis Methods; Short Reports; Stationary phase; Subcellular Processes; Toxins; Tricarboxylic acid cycle; tRNA; Urinary tract; Yellow fluorescent protein; Japan; acyldepsipeptide CFU; isocitrate dehydrogenase; differential interference contrast; toxin-antitoxin; fluorescence-activated cell sorting; acyldepsipeptide; Icd; FACS; TA; colony forming unit DIC; ADEP; fluorescence-activated cell sorting Icd; CFU; differential interference contrast FACS; colony forming unit; isocitrate dehydrogenase TA; toxin-antitoxin WT; wild type; WT; DIC
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3001194

Persisters represent a small subpopulation of non- or slow-growing bacterial cells that are tolerant to killing by antibiotics. Despite their prominent role in the recalcitrance of chronic infections to antibiotic therapy, the mechanism of their formation has remained elusive. We show that sorted cells of Escherichia coli with low levels of energy-generating enzymes are better able to survive antibiotic killing. Using microfluidics time-lapse microscopy and a fluorescent reporter for in vivo ATP measurements, we find that a subpopulation of cells with a low level of ATP survives killing by ampicillin. We propose that these low ATP cells are formed stochastically as a result of fluctuations in the abundance of energy-generating components. These findings point to a general “low energy” mechanism of persister formation.