Title | Inhibition of stationary phase respiration impairs persister formation in E. coli. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Orman, MA, Brynildsen, MP |
Journal | Nat Commun |
Volume | 6 |
Pagination | 7983 |
Date Published | 2015 Aug 06 |
ISSN | 2041-1723 |
Keywords | Bacterial Infections, Cell Culture Techniques, Drug Resistance, Bacterial, Drug Tolerance, Energy Metabolism, Escherichia coli, Oxidation-Reduction, Phenotype, Protein Biosynthesis, Reactive Oxygen Species |
Abstract | <p>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. </p> |
DOI | 10.1038/ncomms8983 |
Alternate Journal | Nat Commun |
PubMed ID | 26246187 |
PubMed Central ID | PMC4530465 |
Grant List | R21 AI105342 / AI / NIAID NIH HHS / United States R21AI105342 / AI / NIAID NIH HHS / United States |