ArticlePLoS pathogens2014
Clonal expansion during Staphylococcus aureus infection dynamics reveals the effect of antibiotic intervention.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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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.
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Who cites it
53 citing papers in PubMed, 87 citations in OpenAlex.
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- Inducible transposon mutagenesis identifies bacterial fitness determinants during infection in mice.Nature microbiology · 2025Article
- Tetracycline and Oxacillin Act Synergistically on Biofilms and Display Increased Efficacy In Vivo Against Staphylococcus aureus.Current microbiology · 2024Article
- Two codependent routes lead to high-level MRSA.Science (New York, N.Y.) · 2024Article
- Experimental evolution ofmBio · 2024Article
- Using the Zebrafish Larval Model of Infection to Investigate Antibiotic Efficacy and Combination Treatments Against Staphylococcus aureus.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Adoptive macrophage directed photodynamic therapy of multidrug-resistant bacterial infection.Nature communications · 2023Article
- Staphylococcus aureus host interactions and adaptation.Nature reviews. Microbiology · 2023Review
- Clonal population expansion of Staphylococcus aureus occurs due to escape from a finite number of intraphagocyte niches.Scientific reports · 2023Article
- Bioactive metabolites ofFrontiers in cellular and infection microbiology · 2023Article
- Antibiotics Limit Adaptation of Drug-Resistant Staphylococcus aureus to Hypoxia.Antimicrobial agents and chemotherapy · 2022Article
- NO-StressedInfection and immunity · 2022Article
- Bayesian Inference of Clonal Expansions in a Dated Phylogeny.Systematic biology · 2022Article
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- Investigating Pathogenicity and Virulence ofInternational journal of molecular sciences · 2021Article
- Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen species.PLoS pathogens · 2021Article
- Modifying TIMER to generate a slow-folding DsRed derivative for optimal use in quickly-dividing bacteria.PLoS pathogens · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
To slow the inexorable rise of antibiotic resistance we must understand how drugs impact on pathogenesis and influence the selection of resistant clones. Staphylococcus aureus is an important human pathogen with populations of antibiotic-resistant bacteria in hospitals and the community. Host phagocytes play a crucial role in controlling S. aureus infection, which can lead to a population "bottleneck" whereby clonal expansion of a small fraction of the initial inoculum founds a systemic infection. Such population dynamics may have important consequences on the effect of antibiotic intervention. Low doses of antibiotics have been shown to affect in vitro growth and the generation of resistant mutants over the long term, however whether this has any in vivo relevance is unknown. In this work, the population dynamics of S. aureus pathogenesis were studied in vivo using antibiotic-resistant strains constructed in an isogenic background, coupled with systemic models of infection in both the mouse and zebrafish embryo. Murine experiments revealed unexpected and complex bacterial population kinetics arising from clonal expansion during infection in particular organs. We subsequently elucidated the effect of antibiotic intervention within the host using mixed inocula of resistant and sensitive bacteria. Sub-curative tetracycline doses support the preferential expansion of resistant microorganisms, importantly unrelated to effects on growth rate or de novo resistance acquisition. This novel phenomenon is generic, occurring with methicillin-resistant S. aureus (MRSA) in the presence of β-lactams and with the unrelated human pathogen Pseudomonas aeruginosa. The selection of resistant clones at low antibiotic levels can result in a rapid increase in their prevalence under conditions that would previously not be thought to favor them. Our results have key implications for the design of effective treatment regimes to limit the spread of antimicrobial resistance, where inappropriate usage leading to resistance may reduce the efficacy of life-saving drugs.
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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.