ArticleAntimicrobial agents and chemotherapy2015
Cellular pharmacokinetics and intracellular activity of the novel peptide deformylase inhibitor GSK1322322 against Staphylococcus aureus laboratory and clinical strains with various resistance phenotypes: studies with human THP-1 monocytes and J774 murine macrophages.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Assessment of the Number and Phenotype of Macrophages in the Human BMB Samples of CML.BioMed research international · 2016Trial
- Antimicrobial Peptides for Skin Wound Healing.Biomolecules · 2025Review
- Biofilm-Associated Candidiasis: Pathogenesis, Prevalence, Challenges and Therapeutic Options.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Biochemistry, Mechanistic Intricacies, and Therapeutic Potential of Antimicrobial Peptides: An Alternative to Traditional Antibiotics.Current medicinal chemistry · 2024Review
- Antimicrobial Peptides Controlling Resistant Bacteria in Animal Production.Frontiers in microbiology · 2022Review
- Ginsenoside 20(S)-Rh2 promotes cellular pharmacokinetics and intracellular antibacterial activity of levofloxacin against Staphylococcus aureus through drug efflux inhibition and subcellular stabilization.Acta pharmacologica Sinica · 2021Article
- Review: Lessons Learned From Clinical Trials Using Antimicrobial Peptides (AMPs).Frontiers in microbiology · 2021Review
- Total synthesis of (±)-fumimycin and analogues for biological evaluation as peptide deformylase inhibitors.Tetrahedron · 2019Article
- Cellular Pharmacokinetics and Intracellular Activity of Gepotidacin against Staphylococcus aureus Isolates with Different Resistance Phenotypes in Models of Cultured Phagocytic Cells.Antimicrobial agents and chemotherapy · 2018Article
- Effective Antimicrobial Activity of Plectasin-Derived Antimicrobial Peptides againstFrontiers in microbiology · 2017Article
- The Inhibition and Resistance Mechanisms of Actinonin, Isolated from Marine Streptomyces sp. NHF165, against Vibrio anguillarum.Frontiers in microbiology · 2016Article
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GSK1322322 is a peptide deformylase inhibitor active against Staphylococcus aureus strains resistant to currently marketed antibiotics. Our aim was to assess the activity of GSK1322322 against intracellular S. aureus using an in vitro pharmacodynamic model and, in parallel, to examine its cellular pharmacokinetics and intracellular disposition. For intracellular activity analysis, we used an established model of human THP-1 monocytes and tested one fully susceptible S. aureus strain (ATCC 25923) and 8 clinical strains with resistance to oxacillin, vancomycin, daptomycin, macrolides, clindamycin, linezolid, or moxifloxacin. Uptake, accumulation, release, and subcellular distribution (cell fractionation) of [(14)C]GSK1322322 were examined in uninfected murine J774 macrophages and uninfected and infected THP-1 monocytes. GSK1322322 demonstrated a uniform activity against the intracellular forms of all S. aureus strains tested, disregarding their resistance phenotypes, with a maximal relative efficacy (E max) of a 0.5 to 1 log10 CFU decrease compared to the original inoculum within 24 h and a static concentration (C s) close to its MIC in broth. Influx and efflux were very fast (<5 min to equilibrium), and accumulation was about 4-fold, with no or a minimal effect of the broad-spectrum eukaryotic efflux transporter inhibitors gemfibrozil and verapamil. GSK1322322 was recovered in the cell-soluble fraction and was dissociated from the main subcellular organelles and from bacteria (in infected cells). The results of this study show that GSK1322322, as a typical novel deformylase inhibitor, may act against intracellular forms of S. aureus. They also suggest that GSK1322322 has the ability to freely diffuse into and out of eukaryotic cells as well as within subcellular compartments.
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