ArticleThe Journal of infectious diseases2013
Alternative mutational pathways to intermediate resistance to vancomycin in methicillin-resistant Staphylococcus aureus.
Article in The Journal of infectious diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- Predictive Value of Vancomycin AUCPharmaceutical research · 2024Article
- Development of a Single-nucleotide Polymorphism Genotyping Assay for the Rapid Detection of Vancomycin-intermediate Resistance inAnnals of laboratory medicine · 2023Article
- Identification and Characterization of a Vancomycin Intermediate-ResistantInfection and drug resistance · 2023Article
- Pharmacokinetics and pharmacodynamics of peptide antibiotics.Advanced drug delivery reviews · 2022Review
- Review
- Optimizing Antimicrobial Drug Dosing in Critically Ill Patients.Microorganisms · 2021Review
- Environmental conditions dictate differential evolution of vancomycin resistance in Staphylococcus aureus.Communications biology · 2021Article
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- The Staphylococcal Cell Wall.Microbiology spectrum · 2019Review
- Antibiotic Resistance and the MRSA Problem.Microbiology spectrum · 2019Review
- Combination Antibiotic Exposure Selectively Alters the Development of Vancomycin Intermediate Resistance in Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2018Article
- Establishing Genotype-to-Phenotype Relationships in Bacteria Causing Hospital-Acquired Pneumonia: A Prelude to the Application of Clinical Metagenomics.Antibiotics (Basel, Switzerland) · 2017Review
- Vancomycin Resistance inThe Yale journal of biology and medicine · 2017Review
- Different Vancomycin-Intermediate Staphylococcus aureus Phenotypes Selected from the Same ST100-hVISA Parental Strain.Microbial drug resistance (Larchmont, N.Y.) · 2017Article
- Article
- Molecular Events for Promotion of Vancomycin Resistance in Vancomycin IntermediateFrontiers in microbiology · 2016Review
- Sequential Evolution of Vancomycin-Intermediate Resistance Alters Virulence in Staphylococcus aureus: Pharmacokinetic/Pharmacodynamic Targets for Vancomycin Exposure.Antimicrobial agents and chemotherapy · 2015Article
- Stepwise decrease in daptomycin susceptibility in clinical Staphylococcus aureus isolates associated with an initial mutation in rpoB and a compensatory inactivation of the clpX gene.Antimicrobial agents and chemotherapy · 2015Article
- High-dose daptomycin therapy for staphylococcal endocarditis and when to apply it.Current infectious disease reports · 2014Article
- Mechanisms of vancomycin resistance in Staphylococcus aureus.The Journal of clinical investigation · 2014Review
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundWe used 2 in vitro experimental systems to compare phenotypic and genotypic changes that accompany selection of mutants of methicillin-resistant Staphylococcus aureus (MRSA) strain JH1 with low-level vancomycin resistance similar to the type found in vancomycin-intermediate S. aureus (VISA).
methodsThe previously described MRSA strain JH1 and its vancomycin-intermediate mutant derivative JH2, both of which were recovered from a patient undergoing vancomycin chemotherapy, were used in this study. Mutants of JH1 were selected in vitro by means of a pharmacokinetic/pharmacodynamic (PK/PD) model of simulated endocardial vegetations (SEVs) and by exposure to vancomycin in laboratory growth medium. Phenotypic abnormalities of JH1 mutants generated by each in vitro experimental system were compared to those of JH2, and whole genomes of 2 in vitro JH1 mutants were sequenced to identify mutations that may be associated with an increased vancomycin minimum inhibitory concentration.
resultsJH1R1 was selected from the PK/PD model, and JH1R2 was selected in laboratory growth medium. Both mutants displayed reduced vancomycin and daptomycin susceptibility and phenotypic alterations (eg, thicker cell walls and abnormal autolysis) that are typical of in vivo VISA mutants. Genome sequencing of JH1R1 identified point mutations in 4 genes, all of which were different from the mutations described in JH2, including 1 mutation in yycG, a component of the WalKR sensory regulatory system. Sequencing of the JH1R2 genome identified mutations in 7 genes, including 2 in rpoB.
conclusionOur findings indicate that JH1 is able to develop VISA-type resistance through several alternative genetic pathways.
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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.