ArticleThe Journal of antimicrobial chemotherapy2021
Impact of PrsA on membrane lipid composition during daptomycin-resistance-mediated β-lactam sensitization in clinical MRSA strains.
Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 13 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
- Genetic Correlates of Synergy Mechanisms of Daptomycin Plus Fosfomycin in Daptomycin-Susceptible and -Resistant Methicillin-ResistantMicroorganisms · 2025Article
- Staphylococcus aureus foldase PrsA contributes to the folding and secretion of protein A.BMC microbiology · 2024Article
- Article
- Enhanced Cell Wall and Cell Membrane Activity Promotes Heat Adaptation ofInternational journal of molecular sciences · 2023Article
- Adaptive Laboratory Evolution ofAntibiotics (Basel, Switzerland) · 2023Article
- Adaptation of Bacteria to Antineoplastic Agents Involves Persister Cells and Increases Resistance to Antibiotics.Bioengineering (Basel, Switzerland) · 2022Article
- Impacts of NaHCOAntibiotics (Basel, Switzerland) · 2022Article
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe cyclic anionic lipopeptide daptomycin is used in the treatment of severe infections caused by Gram-positive pathogens, including MRSA. Daptomycin resistance, although rare, often results in treatment failure. Paradoxically, in MRSA, daptomycin resistance is usually accompanied by a concomitant decrease in β-lactam resistance in what is known as the 'see-saw effect'. This resensitization is extensively used for the treatment of MRSA infections, by combining daptomycin and a β-lactam antibiotic, such as oxacillin.
objectivesWe aimed: (i) to investigate the combined effects of daptomycin and oxacillin on the lipid composition of the cellular membrane of both daptomycin-resistant and -susceptible MRSA strains; and (ii) to assess the involvement of the post-translocational protein PrsA, which plays an important role in oxacillin resistance in MRSA, in membrane lipid composition and remodelling during daptomycin resistance/β-lactam sensitization.
resultsThe combination of microbiological and biochemical studies, with fluorescence microscopy using lipid probes, showed that the lipid composition and surface charge of the daptomycin-resistant cells exposed to daptomycin/oxacillin were dependent on antibiotic concentration and directly associated with PrsA, which influenced cardiolipin remodelling/relocation.
conclusionsOur findings show that PrsA, in addition to its post-transcriptional role in the maturation of PBP 2a, is a key mediator of cell membrane remodelling connected to the see-saw effect and may have a key role in the resensitization of daptomycin-resistant strains to β-lactams, such as oxacillin.
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