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A problem of persistence: still more questions than answers?

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TLDR
Four experts contemplate the main physiological features that define persistence and the implications of persistence for antibiotic treatment regimens, and consider what the study of bacterial persistence has taught us about the heterogeneity of bacterial populations.
Abstract
The current antibiotic resistance crisis has led to increased pressure to prioritize strategies to tackle the issue, with a strong focus being placed on the development of novel antimicrobials. However, one major obstacle that is often overlooked is persister cells, which are refractory to antibiotic treatment. Tackling persistence is a challenge because these cell types are extremely difficult to study and, consequently, little is known about their physiology and the factors that lead to their emergence. Here, four experts contemplate the main physiological features that define persistence and the implications of persistence for antibiotic treatment regimens, and consider what the study of bacterial persistence has taught us about the heterogeneity of bacterial populations.

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Citations
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Antimicrobials: access and sustainable eff ectiveness 2 Understanding the mechanisms and drivers of antimicrobial resistance

TL;DR: To combat the threat to human health and biosecurity from antimicrobial resistance, an understanding of its mechanisms and drivers is needed, and broad ranging, multidisciplinary research is needed across these five levels.
Journal ArticleDOI

Distinguishing between resistance, tolerance and persistence to antibiotic treatment.

TL;DR: This Opinion article describes recent studies of tolerance, resistance and persistence, outlining how a clear and distinct definition for each phenotype can be developed from these findings and proposes a framework for classifying the drug response of bacterial strains according to these definitions that is based on the measurement of the minimum inhibitory concentration.
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Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria

TL;DR: This review summarises both historical and recent scientific data in support of the known biofilm resistance and tolerance mechanisms and suggestions for future work in the field are provided.
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Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies

TL;DR: The mechanism of antibiotic resistance in P. aeruginosa is a recently characterized mechanism, which includes biofilm-mediated resistance and formation of multidrug-tolerant persister cells, and is responsible for recalcitrance and relapse of infections.
References
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Journal ArticleDOI

Bacterial Persistence as a Phenotypic Switch

TL;DR: Investigating the persistence of single cells of Escherichia coli with the use of microfluidic devices found phenotypic switching occurred between normally growing cells and persister cells having reduced growth rates, leading to a simple mathematical description of the persistence switch.
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A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics

TL;DR: The results suggest that all three major classes of bactericidal drugs can be potentiated by targeting bacterial systems that remediate hydroxyl radical damage, including proteins involved in triggering the DNA damage response, e.g., RecA.
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A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations

TL;DR: It is suggested that cancer cell populations employ a dynamic survival strategy in which individual cells transiently assume a reversibly drug-tolerant state to protect the population from eradication by potentially lethal exposures.
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Sublethal Antibiotic Treatment Leads to Multidrug Resistance via Radical-Induced Mutagenesis

TL;DR: It is shown that sublethal levels of bactericidal antibiotics induce mutagenesis, resulting in heterogeneous increases in the minimum inhibitory concentration for a range of antibiotics, irrespective of the drug target.
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