Journal ArticleDOI
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.read more
Citations
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Journal ArticleDOI
Understanding the mechanisms and drivers of antimicrobial resistance
Alison Holmes,Luke S. P. Moore,Arnfinn Sundsfjord,Arnfinn Sundsfjord,Martin Steinbakk,Sadie Regmi,Abhilasha Karkey,Philippe J Guerin,Laura J. V. Piddock +8 more
TL;DR: In this paper, the authors proposed a framework to combat the threat to human health and biosecurity from antimicrobial resistance, an understanding of its mechanisms and drivers is needed.
Antimicrobials: access and sustainable eff ectiveness 2 Understanding the mechanisms and drivers of antimicrobial resistance
Alison Holmes,Luke Sp Moore,Martin Steinbakk,Sadie Regmi,Philippe J Guerin,Laura J. V. Piddock +5 more
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.
Journal ArticleDOI
Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria
Clayton W. Hall,Thien-Fah Mah +1 more
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.
Journal ArticleDOI
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
Nathalie Q. Balaban,Nathalie Q. Balaban,Jack Merrin,Remy Chait,Lukasz Kowalik,Stanislas Leibler +5 more
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.
Journal ArticleDOI
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
Sreenath V. Sharma,Diana Y. Lee,Bihua Li,Margaret P. Quinlan,Fumiyuki Takahashi,Shyamala Maheswaran,Ultan McDermott,Nancy Azizian,Lee Zou,Michael A. Fischbach,Kwok-Kin Wong,Kathleyn A. Brandstetter,Ben S. Wittner,Sridhar Ramaswamy,Marie Classon,Jeff Settleman +15 more
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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Treatment of staphylococcal infections with penicillin by intermittent sterilisation
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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.