ArticleAntimicrobial agents and chemotherapy2015
A novel point mutation promotes growth phase-dependent daptomycin tolerance in Staphylococcus aureus.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 106 citations in OpenAlex.
- Article
- Reduced ROS-associated prophage induction in a lepA mutant contributes to increased fluoroquinolone persistence in Salmonella Typhimurium.Scientific reports · 2026Article
- Multiple clades of regulators contribute to bacterial phosphate homeostasis and pathogenesis.bioRxiv : the preprint server for biology · 2025Article
- Increased Expression of AbcA Efflux Pump Accelerated Resistance Development from Tolerance to Resistance Against Oxacillin inMicroorganisms · 2025Article
- The mutational landscape of Staphylococcus aureus during colonisation.Nature communications · 2025Article
- Antibiotic tolerance among clinical isolates: mechanisms, detection, prevalence, and significance.Clinical microbiology reviews · 2024Review
- Intrinsic antimicrobial resistance: Molecular biomaterials to combat microbial biofilms and bacterial persisters.Biomaterials · 2024Review
- Laboratory Evolution of Antimicrobial Resistance in Bacteria to Develop Rational Treatment Strategies.Antibiotics (Basel, Switzerland) · 2024Review
- Antibiotic dose and nutrient availability differentially drive the evolution of antibiotic resistance and persistence.The ISME journal · 2024Article
- Pleiotropic cellular responses underlying antibiotic tolerance inFrontiers in microbiology · 2024Article
- The Bacterial Biofilms: Formation, Impacts, and Possible Management Targets in the Healthcare System.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2024Review
- Contribution of the SOS response and the DNA repair systems to norfloxacin induced mutations inMarine life science & technology · 2023Article
- Intermittent antibiotic treatment of bacterial biofilms favors the rapid evolution of resistance.Communications biology · 2023Article
- Comparative Genomics Identifies Novel Genetic Changes Associated with Oxacillin, Vancomycin and Daptomycin Susceptibility in ST100 Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2023Article
- Evolution and Emergence of Antibiotic Resistance in Given Ecosystems: Possible Strategies for Addressing the Challenge of Antibiotic Resistance.Antibiotics (Basel, Switzerland) · 2022Review
- The Development of Technology to Prevent, Diagnose, and Manage Antimicrobial Resistance in Healthcare-Associated Infections.Vaccines · 2022Review
- PurN Is Involved in Antibiotic Tolerance and Virulence inAntibiotics (Basel, Switzerland) · 2022Article
- Tolerance to Ceftriaxone inAntibiotics (Basel, Switzerland) · 2022Article
- Impact of Environmental Conditions on the Protein Content ofMicroorganisms · 2022Article
- Mutation in the Two-Component System Regulator YycH Leads to Daptomycin Tolerance in Methicillin-Resistant Staphylococcus aureus upon Evolution with a Population Bottleneck.Microbiology spectrum · 2022Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recalcitrance of genetically susceptible bacteria to antibiotic killing is a hallmark of bacterial drug tolerance. This phenomenon is prevalent in biofilms, persisters, and also planktonic cells and is associated with chronic or relapsing infections with pathogens such as Staphylococcus aureus. Here we report the in vitro evolution of an S. aureus strain that exhibits a high degree of nonsusceptibility to daptomycin as a result of cyclic challenges with bactericidal concentrations of the drug. This phenotype was attributed to stationary growth phase-dependent drug tolerance and was clearly distinguished from resistance. The underlying genetic basis was revealed to be an adaptive point mutation in the putative inorganic phosphate (Pi) transporter gene pitA. Drug tolerance caused by this allele, termed pitA6, was abrogated when the upstream gene pitR was inactivated. Enhanced tolerance toward daptomycin, as well as the acyldepsipeptide antibiotic ADEP4 and various combinations of other drugs, was accompanied by elevated intracellular concentrations of Pi and polyphosphate, which may reversibly interfere with critical cellular functions. The evolved strain displayed increased rates of survival within human endothelial cells, demonstrating the correlation of intracellular persistence and drug tolerance. These findings will be useful for further investigations of S. aureus drug tolerance, toward the development of additional antipersister compounds and strategies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.