Prevalence of Antibiotic Tolerance and Risk for Reinfection Among Escherichia coli Bloodstream Isolates: A Prospective Cohort Study.

Background: Tolerance is the ability of bacteria to survive transient exposure to high concentrations of a bactericidal antibiotic without a change in the minimal inhibitory concentration, thereby limiting the efficacy of antimicrobials. The study sought to determine the prevalence of tolerance in a prospective cohort of E. coli bloodstream infection and to explore the association of tolerance with reinfection risk.

Observation of universal ageing dynamics in antibiotic persistence.

Stress responses allow cells to adapt to changes in external conditions by activating specific pathways. Here we investigate the dynamics of single cells that were subjected to acute stress that is too strong for a regulated response but not lethal. We show that when the growth of bacteria is arrested by acute transient exposure to strong inhibitors, the statistics of their regrowth dynamics can be predicted by a model for the cellular network that ignores most of the details of the underlying molecular interactions.

Effect of tolerance on the evolution of antibiotic resistance under drug combinations.

Drug combinations are widely used in clinical practice to prevent the evolution of resistance. However, little is known about the effect of tolerance, a different mode of survival, on the efficacy of drug combinations for preventing the evolution of resistance. In this work, we monitored strains evolving in patients under treatment.

Epistasis between antibiotic tolerance, persistence, and resistance mutations.

Understanding the evolution of microorganisms under antibiotic treatments is a burning issue. Typically, several resistance mutations can accumulate under antibiotic treatment, and the way in which resistance mutations interact, i.e.

Antibiotic tolerance facilitates the evolution of resistance.

Controlled experimental evolution during antibiotic treatment can help to explain the processes leading to antibiotic resistance in bacteria. Recently, intermittent antibiotic exposures have been shown to lead rapidly to the evolution of tolerance-that is, the ability to survive under treatment without developing resistance. However, whether tolerance delays or promotes the eventual emergence of resistance is unclear.

A long-term epigenetic memory switch controls bacterial virulence bimodality.

When pathogens enter the host, sensing of environmental cues activates the expression of virulence genes. Opposite transition of pathogens from activating to non-activating conditions is poorly understood. Interestingly, variability in the expression of virulence genes upon infection enhances colonization.

Systematic identification and quantification of phase variation in commensal and pathogenic Escherichia coli.

Bacteria have been shown to generate constant genetic variation in a process termed phase variation. We present a tool based on whole genome sequencing that allows detection and quantification of coexisting genotypes mediated by genomic inversions in bacterial cultures. We tested our method on widely used strains of Escherichia coli, and detected stable and reproducible phase variation in several invertible loci.

Optimization of lag time underlies antibiotic tolerance in evolved bacterial populations.

The great therapeutic achievements of antibiotics have been dramatically undercut by the evolution of bacterial strategies that overcome antibiotic stress. These strategies fall into two classes. 'Resistance' makes it possible for a microorganism to grow in the constant presence of the antibiotic, provided that the concentration of the antibiotic is not too high.

Direct observation of single stationary-phase bacteria reveals a surprisingly long period of constant protein production activity.

Exponentially growing bacteria are rarely found in the wild, as microorganisms tend to spend most of their lifetime at stationary phase. Despite this general prevalence of stationary-phase bacteria, they are as yet poorly characterized. Our goal was to quantitatively study this phase by direct observation of single bacteria as they enter into stationary phase and by monitoring their activity over several days during growth arrest.

HipA-mediated antibiotic persistence via phosphorylation of the glutamyl-tRNA-synthetase.

Bacterial persistence has been shown to be an underlying factor in the failure of antibiotic treatments. Although many pathways, among them the stringent response and toxin-antitoxin modules, have been linked to antibiotic persistence, a clear molecular mechanism for the growth arrest that characterizes persistent bacteria remained elusive. Here, we screened an expression library for putative targets of HipA, the first toxin linked to persistence, and a serine/threonine kinase.

Automated imaging with ScanLag reveals previously undetectable bacterial growth phenotypes.

We developed an automated system, ScanLag, that measures in parallel the delay in growth (lag time) and growth rate of thousands of cells. Using ScanLag, we detected small subpopulations of bacteria with dramatically increased lag time upon starvation. By screening a library of Escherichia coli deletion mutants, we achieved two-dimensional mapping of growth characteristics, which showed that ScanLag enables multidimensional screens for quantitative characterization and identification of rare phenotypic variants.

Regulation of phenotypic variability by a threshold-based mechanism underlies bacterial persistence.

In the face of antibiotics, bacterial populations avoid extinction by harboring a subpopulation of dormant cells that are largely drug insensitive. This phenomenon, termed "persistence," is a major obstacle for the treatment of a number of infectious diseases. The mechanism that generates both actively growing as well as dormant cells within a genetically identical population is unknown.