ArticleAntimicrobial agents and chemotherapy2007
Modulation of the cellular accumulation and intracellular activity of daptomycin towards phagocytized Staphylococcus aureus by the P-glycoprotein (MDR1) efflux transporter in human THP-1 macrophages and madin-darby canine kidney cells.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 55 citations in OpenAlex.
- Effect of antibiotics on Kupffer cell immunometabolism relative to intracellular killing ofmBio · 2025Article
- Comparative in vitro efficacy of antibiotics against the intracellular reservoir of Staphylococcus aureus.The Journal of antimicrobial chemotherapy · 2024Article
- Daptomycin Physiology-Based Pharmacokinetic Modeling to Predict Drug Exposure and Pharmacodynamics in Skin and Bone Tissues.Clinical pharmacokinetics · 2022Article
- Intracellular Accumulation of Novel and Clinically Used TB Drugs Potentiates Intracellular Synergy.Microbiology spectrum · 2021Article
- Review
- Clinical Pharmacokinetics of Daptomycin.Clinical pharmacokinetics · 2021Review
- Pharmacogenomics of Antibiotics.International journal of molecular sciences · 2020Review
- Comparison of the Drug-Drug Interaction Potential of Daptomycin in Combination with Rifampin in Healthy Adult Volunteers.Antimicrobial agents and chemotherapy · 2018Article
- Activities of Combinations of Antistaphylococcal Antibiotics with Fusidic Acid against Staphylococcal Biofilms inAntimicrobial agents and chemotherapy · 2018Article
- Topical Treatment for Cutaneous Leishmaniasis: Dermato-Pharmacokinetic Lead Optimization of Benzoxaboroles.Antimicrobial agents and chemotherapy · 2018Article
- Up-regulation of ATP-binding cassette transporters in the THP-1 human macrophage cell line by the antichagasic benznidazole.Memorias do Instituto Oswaldo Cruz · 2016Article
- Review
- Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics.Clinical pharmacokinetics · 2016Review
- Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms.International journal of nanomedicine · 2015Article
- Unique functional and structural properties of the LRRK2 protein ATP-binding pocket.The Journal of biological chemistry · 2014Article
- Article
- A 30-years review on pharmacokinetics of antibiotics: is the right time for pharmacogenetics?Current drug metabolism · 2014Review
- Let-7 modulates acquired resistance of ovarian cancer to Taxanes via IMP-1-mediated stabilization of multidrug resistance 1.International journal of cancer · 2012Article
- Daptomycin: local application in implant-associated infection and complicated osteomyelitis.TheScientificWorldJournal · 2012Article
- Cellular pharmacokinetics of the novel biaryloxazolidinone radezolid in phagocytic cells: studies with macrophages and polymorphonuclear neutrophils.Antimicrobial agents and chemotherapy · 2010Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
P-glycoprotein (P-gp; MDR1), a major efflux transporter, recognizes various antibiotics and is present in macrophages. We have examined its effect on the modulation of the intracellular accumulation and activity of daptomycin towards phagocytized Staphylococcus aureus (ATCC 25923) in human THP-1 macrophages, in comparison with MDCK epithelial cells (wild type and MDCK-MDR1 overexpressing P-gp; the bulk of the protein was immunodetected at the surface of all three cell types). Daptomycin displayed concentration-dependent intracellular activity (Hill equation pattern) in THP-1 and MDCK cells with (i) 50% effective drug extracellular concentration (EC(50); relative potency) and static concentrations at 9 to 10 times the MIC and (ii) maximal efficacy (E(max); CFU decrease at infinite extracellular drug concentration) at 1.6 to 2 log compared to that of the postphagocytosis inoculum. Verapamil (100 microM) and elacridar (GF 120918; 0.5 microM), two known inhibitors of P-gp, decreased daptomycin EC(50) (about threefold) in THP-1 and MDCK cells without affecting E(max). Daptomycin EC(50) was about three- to fourfold higher and accumulation in MDCK-MDR1 commensurately lower than in wild-type cells. In THP-1 macrophages, (i) verapamil and ATP depletion increased, and ouabain (an inducer of mdr1 [the gene encoding P-gp] expression) decreased the accumulation of daptomycin in parallel with that of DiOC(2) (a known substrate of P-gp); (ii) silencing mdr1 with duplex human mdr1 siRNAs reduced the cell content in immunoreactive P-gp to 15 to 30% of controls and caused an eight- to 13-fold increase in daptomycin accumulation. We conclude that daptomycin is subject to efflux from THP-1 macrophages and MDCK cells by P-gp, which reduces its intracellular activity against phagocytized S. aureus.
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