ArticlePLoS pathogens2011
Evolution of multidrug resistance during Staphylococcus aureus infection involves mutation of the essential two component regulator WalKR.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers.
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Who cites it
204 citing papers in PubMed, 378 citations in OpenAlex.
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- Polygenic, cell-envelope adaptations drive high-frequency daptomycin resistance inAntimicrobial agents and chemotherapy · 2026Article
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- Genomic and phenotypic adaptations of methicillin resistant Staphylococcus aureus during vancomycin therapy.Scientific reports · 2025Article
- Simulated exposures of oritavancin in in vitro pharmacodynamic models select for methicillin-resistant Staphylococcus aureus with reduced susceptibility to oritavancin but minimal cross-resistance or seesaw effect with other antimicrobials.The Journal of antimicrobial chemotherapy · 2025Article
- Mechanism of antibacterial and antibiofilm of thiazolidinone derivative TD-H2-A against Staphylococcus aureus.Scientific reports · 2025Article
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- Regulatory dynamics of arginine metabolism in Staphylococcus aureus.Biochemical Society transactions · 2024Review
- Synergistic potential of LeuBMC microbiology · 2024Article
- AVR/I/SSAPDB: a comprehensive & specialised knowledgebase of antimicrobial peptides to combat VRSA, VISA, and VSSA.World journal of microbiology & biotechnology · 2024Article
- Unraveling novel mutation patterns and morphological variations in two dalbavancin-resistant MRSA strains in Austria using whole genome sequencing and transmission electron microscopy.BMC infectious diseases · 2024Article
- Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA.Nature communications · 2024Article
144 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antimicrobial resistance in Staphylococcus aureus is a major public health threat, compounded by emergence of strains with resistance to vancomycin and daptomycin, both last line antimicrobials. Here we have performed high throughput DNA sequencing and comparative genomics for five clinical pairs of vancomycin-susceptible (VSSA) and vancomycin-intermediate ST239 S. aureus (VISA); each pair isolated before and after vancomycin treatment failure. These comparisons revealed a frequent pattern of mutation among the VISA strains within the essential walKR two-component regulatory locus involved in control of cell wall metabolism. We then conducted bi-directional allelic exchange experiments in our clinical VSSA and VISA strains and showed that single nucleotide substitutions within either walK or walR lead to co-resistance to vancomycin and daptomycin, and caused the typical cell wall thickening observed in resistant clinical isolates. Ion Torrent genome sequencing confirmed no additional regulatory mutations had been introduced into either the walR or walK VISA mutants during the allelic exchange process. However, two potential compensatory mutations were detected within putative transport genes for the walK mutant. The minimal genetic changes in either walK or walR also attenuated virulence, reduced biofilm formation, and led to consistent transcriptional changes that suggest an important role for this regulator in control of central metabolism. This study highlights the dramatic impacts of single mutations that arise during persistent S. aureus infections and demonstrates the role played by walKR to increase drug resistance, control metabolism and alter the virulence potential of this pathogen.
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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.