ATP-Dependent Persister Formation in Escherichia Coli

Overview

Journal mBio

Publisher American Society for Microbiology

Specialty Microbiology

Date 2017 Feb 9

PMID 28174313

Citations 221

Authors

Yue Shan

Autumn Brown Gandt

Sarah E Rowe

Julia P Deisinger

Brian P Conlon

Kim Lewis

Affiliations

Soon will be listed here.

Abstract

Importance: Persisters are a subpopulation of antibiotic-tolerant cells responsible for the recalcitrance of chronic infections. Our current understanding of persister formation is primarily based on studies of E. coli The activation of toxin-antitoxin systems by ppGpp has become a widely accepted model for persister formation. In this study, we found that stress-induced activation of mRNA interferase-type toxins does not necessarily cause persister formation. We also found that the persister marker rrnB P1 reports persister cells because it detects a drop in cellular ATP levels. Consistent with this, lowering the ATP level decreases antibiotic target activity and, thus, leads to persister formation. We conclude that stochastic variation in ATP is the main mechanism of persister formation. A decrease in ATP provides a satisfactory explanation for the drug tolerance of persisters, since bactericidal antibiotics act by corrupting energy-dependent targets.

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