ArticleProceedings of the National Academy of Sciences of the United States of America2007
Tracking the in vivo evolution of multidrug resistance in Staphylococcus aureus by whole-genome sequencing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 298 papers.
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Who cites it
298 citing papers in PubMed, 542 citations in OpenAlex.
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- Genomics for antimicrobial resistance-progress and future directions.Antimicrobial agents and chemotherapy · 2025Review
- Genomic and phenotypic adaptations of methicillin resistant Staphylococcus aureus during vancomycin therapy.Scientific reports · 2025Article
- Evaluation of the Use of Preventive Antibiotic Therapy in Patients Undergoing One-Step Prosthetic Revision Surgery with Low Preoperative Infectious Risk.Antibiotics (Basel, Switzerland) · 2025Article
- Diabetes potentiates the emergence and expansion of antibiotic resistance.Science advances · 2025Article
- Mechanisms of Staphylococcus aureus Antibiotics Resistance Revealed by Adaptive Laboratory Evolution.Current microbiology · 2025Article
- Emerging Antimicrobial Strategies Against Heterogeneous and Vancomycin-IntermediateInternational journal of general medicine · 2025Review
- The Use of Next-Generation Sequencing in Personalized Medicine.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Emergence of carbapenem resistance in persistent Shewanella algae bacteremia: the role of pdsS G547W mutation in adaptive subpopulation dynamics.Annals of clinical microbiology and antimicrobials · 2024Article
- From Petri Dishes to Patients to Populations: Scales and Evolutionary Mechanisms Driving Antibiotic Resistance.Annual review of microbiology · 2024Review
- Ecological and evolutionary mechanisms driving within-patient emergence of antimicrobial resistance.Nature reviews. Microbiology · 2024Review
- Comparison of Multiple Carbapenemase Tests Based on an Unbiased Colony-Selection Method.Biomedicines · 2024Article
- ST105 Lineage of MRSA: An Emerging Implication for Bloodstream Infection in the American and European Continents.Antibiotics (Basel, Switzerland) · 2024Review
- Triple threat: how diabetes results in worsened bacterial infections.Infection and immunity · 2024Review
- Bacterial persisters: molecular mechanisms and therapeutic development.Signal transduction and targeted therapy · 2024Review
238 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
Abstract
The spread of multidrug-resistant Staphylococcus aureus (MRSA) strains in the clinical environment has begun to pose serious limits to treatment options. Yet virtually nothing is known about how resistance traits are acquired in vivo. Here, we apply the power of whole-genome sequencing to identify steps in the evolution of multidrug resistance in isogenic S. aureus isolates recovered periodically from the bloodstream of a patient undergoing chemotherapy with vancomycin and other antibiotics. After extensive therapy, the bacterium developed resistance, and treatment failed. Sequencing the first vancomycin susceptible isolate and the last vancomycin nonsusceptible isolate identified genome wide only 35 point mutations in 31 loci. These mutations appeared in a sequential order in isolates that were recovered at intermittent times during chemotherapy in parallel with increasing levels of resistance. The vancomycin nonsusceptible isolates also showed a 100-fold decrease in susceptibility to daptomycin, although this antibiotic was not used in the therapy. One of the mutated loci associated with decreasing vancomycin susceptibility (the vraR operon) was found to also carry mutations in six additional vancomycin nonsusceptible S. aureus isolates belonging to different genetic backgrounds and recovered from different geographic sites. As costs drop, whole-genome sequencing will become a useful tool in elucidating complex pathways of in vivo evolution in bacterial pathogens.
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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.