Inhibition of stationary phase respiration impairs persister formation in E. coli.

TitleInhibition of stationary phase respiration impairs persister formation in E. coli.
Publication TypeJournal Article
Year of Publication2015
AuthorsOrman, MA, Brynildsen, MP
JournalNat Commun
Volume6
Pagination7983
Date Published2015 08 06
ISSN2041-1723
KeywordsBacterial Infections, Cell Culture Techniques, Drug Resistance, Bacterial, Drug Tolerance, Energy Metabolism, Escherichia coli, Oxidation-Reduction, Phenotype, Protein Biosynthesis, Reactive Oxygen Species
Abstract

Bacterial persisters are rare phenotypic variants that temporarily tolerate high antibiotic concentrations. Persisters have been hypothesized to underlie the recalcitrance of biofilm infections, and strategies to eliminate these cells have the potential to improve treatment outcomes for many hospital-treated infections. Here we investigate the role of stationary phase metabolism in generation of type I persisters in Escherichia coli, which are those that are formed by passage through stationary phase. We find that persisters are unlikely to derive from bacteria with low redox activity, and that inhibition of respiration during stationary phase reduces persister levels by up to ∼1,000-fold. Loss of stationary phase respiratory activity prevents digestion of endogenous proteins and RNA, which yields bacteria that are more capable of translation, replication and concomitantly cell death when exposed to antibiotics. These findings establish bacterial respiration as a prime target for reducing the number of persisters formed in nutrient-depleted, non-growing populations.

DOI10.1038/ncomms8983
Alternate JournalNat Commun
PubMed ID26246187
PubMed Central IDPMC4530465
Grant ListR21 AI105342 / AI / NIAID NIH HHS / United States
R21AI105342 / AI / NIAID NIH HHS / United States