ArticleAntimicrobial agents and chemotherapy2012
VraSR two-component regulatory system contributes to mprF-mediated decreased susceptibility to daptomycin in in vivo-selected clinical strains of methicillin-resistant Staphylococcus aureus.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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77 citing papers in PubMed, 126 citations in OpenAlex.
- Restoration of daptomycin sensitivity with adjunctive cefazolin is associated with C-terminal MprF mutations in MRSA bacteremia isolates.Antimicrobial agents and chemotherapy · 2026Article
- The staphylococcal type VII secretion system protein EsxC impacts daptomycin sensitivity through controlling bacterial cell envelope integrity.Journal of bacteriology · 2026Article
- Staphylococcus aureus sensor histidine kinase VraS mutations linked to antibiotic resistance affect enzymatic catalysis, stability, and substrate interactions.Archives of biochemistry and biophysics · 2026Article
- Acquisition of daptomycin resistance in patients results in decreased virulence inInfection and immunity · 2025Article
- Characterisation ofJAC-antimicrobial resistance · 2025Article
- Staphylococcal Drug Resistance: Mechanisms, Therapies, and Nanoparticle Interventions.Infection and drug resistance · 2025Review
- Identification ofJournal of bacteriology · 2024Article
- Genomic Insights intoPathogens (Basel, Switzerland) · 2024Article
- Deciphering agr quorum sensing in Staphylococcus aureus: insights and therapeutic prospects.Molecular biology reports · 2024Review
- Staph wars: the antibiotic pipeline strikes back.Microbiology (Reading, England) · 2023Review
- NH125 Sensitizes Staphylococcus aureus to Cell Wall-Targeting Antibiotics through the Inhibition of the VraS Sensor Histidine Kinase.Microbiology spectrum · 2023Article
- Adaptive Laboratory Evolution ofAntibiotics (Basel, Switzerland) · 2023Article
- Impact of Bicarbonate on PBP2a Production, Maturation, and Functionality in Methicillin-ResistantAntimicrobial agents and chemotherapy · 2023Article
- Erythritol alters phosphotransferase gene expression and inhibits theFrontiers in veterinary science · 2023Article
- Vancomycin Resistance inMicroorganisms · 2022Review
- Review
- Molecular Basis of Non-β-Lactam Antibiotics Resistance inAntibiotics (Basel, Switzerland) · 2022Review
- Molecular Mechanisms of Drug Resistance inInternational journal of molecular sciences · 2022Review
- Bacterial cell membranes and their role in daptomycin resistance: A review.Frontiers in molecular biosciences · 2022Review
- Antibacterial activity of novel linear polyamines againstFrontiers in microbiology · 2022Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Daptomycin (DAP) is a new class of cyclic lipopeptide antibiotic highly active against methicillin-resistant Staphylococcus aureus (MRSA) infections. Proposed mechanisms involve disruption of the functional integrity of the bacterial membrane in a Ca-dependent manner. In the present work, we investigated the molecular basis of DAP resistance in a group of isogenic MRSA clinical strains obtained from patients with S. aureus infections after treatment with DAP. Different point mutations were found in the mprF gene in DAP-resistant (DR) strains. Investigation of the mprF L826F mutation in DR strains was accomplished by inactivation and transcomplementation of either full-length wild-type or mutated mprF in DAP-susceptible (DS) strains, revealing that they were mechanistically linked to the DR phenotype. However, our data suggested that mprF was not the only factor determining the resistance to DAP. Differential gene expression analysis showed upregulation of the two-component regulatory system vraSR. Inactivation of vraSR resulted in increased DAP susceptibility, while complementation of vraSR mutant strains restored DAP resistance to levels comparable to those observed in the corresponding DR wild-type strain. Electron microscopy analysis showed a thicker cell wall in DR CB5012 than DS CB5011, an effect that was related to the impact of vraSR and mprF mutations in the cell wall. Moreover, overexpression of vraSR in DS strains resulted in both increased resistance to DAP and decreased resistance to oxacillin, similar to the phenotype observed in DR strains. These results support the suggestion that, in addition to mutations in mprF, vraSR contributes to DAP resistance in the present group of clinical strains.
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