ArticleAntimicrobial agents and chemotherapy2013
Causal role of single nucleotide polymorphisms within the mprF gene of Staphylococcus aureus in daptomycin resistance.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57 citing papers in PubMed, 93 citations in OpenAlex.
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- Use of Daptomycin to Manage Severe MRSA Infections in Humans.Antibiotics (Basel, Switzerland) · 2025Review
- Acquisition of daptomycin resistance in patients results in decreased virulence inInfection and immunity · 2025Article
- Daptomycin forms a stable complex with phosphatidylglycerol for selective uptake to bacterial membrane.eLife · 2025Article
- Molecular Mechanisms of Bacterial Resistance to Antimicrobial Peptides in the Modern Era: An Updated Review.Microorganisms · 2024Review
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- Population Analysis of Daptomycin-non-Susceptible Methicillin-Resistant Staphylococcus aureus Reveals the Presence of Variants That Contribute to Daptomycin Resistance.Current microbiology · 2024Article
- Boosting Fitness Costs Associated with Antibiotic Resistance in the Gut: On the Way to Biorestoration of Susceptible Populations.Biomolecules · 2024Review
- Phenotypic and genetic characterization of daptomycin non-susceptibleFrontiers in cellular and infection microbiology · 2024Article
- Known mechanisms cannot account for a third of reduced susceptibility in non-aureus staphylococci.npj antimicrobials and resistance · 2023Article
- Antimicrobial resistance in methicillin-resistant staphylococcus aureus.Saudi journal of biological sciences · 2023Review
- Occurrence ofAntibiotics (Basel, Switzerland) · 2023Article
- Polymyxin and lipopeptide antibiotics: membrane-targeting drugs of last resort.Microbiology (Reading, England) · 2022Review
- The Role ofAntimicrobial agents and chemotherapy · 2022Article
- Role of the Staphylococcus aureus Extracellular Loop of GraS in Resistance to Distinct Human Defense Peptides in PMN and Invasive Cardiovascular infections.Infection and immunity · 2021Article
- β-Lactam-Induced Cell Envelope Adaptations, Not Solely Enhanced Daptomycin Binding, Underlie Daptomycin-β-Lactam Synergy in Methicillin-Resistant Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2021Article
- Phospholipid translocation captured in a bifunctional membrane protein MprF.Nature communications · 2021Article
- Comparative genomics ofMicrobial genomics · 2021Article
- Genomic Insights Into Last-Line Antimicrobial Resistance in Multidrug-ResistantFrontiers in microbiology · 2021Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Single nucleotide polymorphisms (SNPs) within the mprF open reading frame (ORF) have been commonly observed in daptomycin-resistant (DAP(r)) Staphylococcus aureus strains. Such SNPs are usually associated with a gain-in-function phenotype, in terms of either increased synthesis or enhanced translocation (flipping) of lysyl-phosphatidylglycerol (L-PG). However, it is unclear if such mprF SNPs are causal in DAP(r) strains or are merely a biomarker for this phenotype. In this study, we used an isogenic set of S. aureus strains: (i) Newman, (ii) its isogenic ΔmprF mutant, and (iii) several in trans plasmid complementation constructs, expressing either a wild-type or point-mutated form of the mprF ORF cloned from two isogenic DAP-susceptible (DAP(s))-DAP(r) strain pairs (616-701 and MRSA11/11-REF2145). Complementation of the ΔmprF strain with singly point-mutated mprF genes (mprFS295L or mprFT345A) revealed that (i) individual and distinct point mutations within the mprF ORF can recapitulate phenotypes observed in donor strains (i.e., changes in DAP MICs, positive surface charge, and cell membrane phospholipid profiles) and (ii) these gain-in-function SNPs (i.e., enhanced L-PG synthesis) likely promote reduced DAP binding to S. aureus by a charge repulsion mechanism. Thus, for these two DAP(r) strains, the defined mprF SNPs appear to be causally related to this phenotype.
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