RRC ID 56356
Author Yamamoto N, Isshiki R, Kawai Y, Tanaka D, Sekiguchi T, Matsumoto S, Tsuneda S.
Title Stochastic expression of lactate dehydrogenase A induces Escherichia coli persister formation.
Journal J Biosci Bioeng
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.
Volume 126(1)
Pages 30-37
Published 2018-7-1
DOI 10.1016/j.jbiosc.2018.01.016
PII S1389-1723(17)31004-6
PMID 29449156
MeSH Anti-Bacterial Agents / pharmacology Drug Resistance, Bacterial / genetics* Energy Metabolism / drug effects Energy Metabolism / genetics Escherichia coli / drug effects Escherichia coli / genetics* Escherichia coli / physiology Escherichia coli Proteins / genetics Gene Expression Regulation, Bacterial Gene Expression Regulation, Enzymologic / physiology Isoenzymes / genetics L-Lactate Dehydrogenase / genetics* Lactate Dehydrogenase 5 Phenotype Transcriptional Activation / drug effects
IF 2.032
Times Cited 3
Prokaryotes E. coli Keio JW1375 Keio JW1908