Stochastic expression of lactate dehydrogenase A induces Escherichia coli persister formation

Naoki Yamamoto, Rino Isshiki, Yuto Kawai, Daiki Tanaka, Tetsushi Sekiguchi, Shinya Matsumoto, Satoshi Tsuneda

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Bacterial persisters are phenotypic variants that survive the treatment of lethal doses of growth-targeting antibiotics without mutations. Although the mechanism underlying persister formation has been studied for decades, how the persister phenotype is switched on and protects itself from antibiotics has been elusive. In this study, we focused on the lactate dehydrogenase gene (ldhA) that was upregulated in an Escherichia coli persister-enriched population. A survival rate assay using an ldhA-overexpressing strain showed that ldhA expression induced persister formation. To identify ldhA-mediated persister formation at the single-cell level, time-lapse microscopy with a microfluidic device was used. Stochastic ldhA expression was found to induce dormancy and tolerance against high-dose ampicillin treatment (500 μg/ml). To better understand the underlying mechanism, we investigated the relationship between ldhA-mediated persister formation and previously reported persister formation through aerobic metabolism repression. As a result, ldhA expression enhanced the proton motive force (PMF) and ATP synthesis. These findings suggest that ldhA-mediated persister formation pathway is different from previously reported persister formation via repression of aerobic metabolism.

Original languageEnglish
JournalJournal of Bioscience and Bioengineering
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

L-Lactate Dehydrogenase
Escherichia coli
Genes
Gene expression
Antibiotics
Lab-On-A-Chip Devices
Gene Expression
Metabolism
Anti-Bacterial Agents
Proton-Motive Force
lactate dehydrogenase 5
Oxidoreductases
Adenosinetriphosphate
Ampicillin
Microfluidics
Protons
Microscopy
Assays
Microscopic examination
Adenosine Triphosphate

Keywords

  • Energy metabolism
  • Escherichia coli
  • ldhA
  • Microfluidic device
  • Persister
  • Proton motive force
  • Single cell
  • Stochastic expression

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Stochastic expression of lactate dehydrogenase A induces Escherichia coli persister formation. / Yamamoto, Naoki; Isshiki, Rino; Kawai, Yuto; Tanaka, Daiki; Sekiguchi, Tetsushi; Matsumoto, Shinya; Tsuneda, Satoshi.

In: Journal of Bioscience and Bioengineering, 01.01.2018.

Research output: Contribution to journalArticle

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AU - Isshiki, Rino

AU - Kawai, Yuto

AU - Tanaka, Daiki

AU - Sekiguchi, Tetsushi

AU - Matsumoto, Shinya

AU - Tsuneda, Satoshi

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