ArticleThe Journal of infectious diseases2013
Pharmacokinetics of posaconazole within epithelial cells and fungi: insights into potential mechanisms of action during treatment and prophylaxis.
Article in The Journal of infectious diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- Azole drugs have differential efficacy in varied models of immunosuppression in larval zebrafish hosts.Future microbiology · 2025Article
- Pulmonary surfactant impacts in vitro activity of selected antifungal drugs against Candida krusei and Candida albicans.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2024Article
- Is theMicroorganisms · 2023Article
- Tackling the emerging threat of antifungal resistance to human health.Nature reviews. Microbiology · 2022Review
- Longitudinal multimodal imaging-compatible mouse model of triazole-sensitive and -resistant invasive pulmonary aspergillosis.Disease models & mechanisms · 2022Article
- Marginating transitional B cells modulate neutrophils in the lung during inflammation and pneumonia.The Journal of experimental medicine · 2021Article
- The Role of New Posaconazole Formulations in the Treatment of Candida albicans Infections: Data from anAntimicrobial agents and chemotherapy · 2021Article
- Galectin-3 enhances neutrophil motility and extravasation into the airways during Aspergillus fumigatus infection.PLoS pathogens · 2020Article
- Efficacy of Voriconazole against Aspergillus fumigatus Infection Depends on Host Immune Function.Antimicrobial agents and chemotherapy · 2020Article
- Therapeutic Challenges of Non-Antimicrobial agents and chemotherapy · 2019Review
- Beyond tissue concentrations: antifungal penetration at the site of infection.Medical mycology · 2019Review
- A strategy for designing voriconazole dosage regimens to prevent invasive pulmonary aspergillosis based on a cellular pharmacokinetics/pharmacodynamics model.Journal of translational medicine · 2018Article
- Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients.Infection · 2017Review
- Urinary tract aspergillosis in a patient with chronic kidney disease.BMJ case reports · 2017Article
- Genome-wide mutagenesis and multi-drug resistance in American trypanosomes induced by the front-line drug benznidazole.Scientific reports · 2017Article
- Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Posaconazole-Loaded Leukocytes as a Novel Treatment Strategy Targeting Invasive Pulmonary Aspergillosis.The Journal of infectious diseases · 2017Article
- Posaconazole Plasma Concentrations on Days Three to Five Predict Steady-State Levels.Antimicrobial agents and chemotherapy · 2016Article
- Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections.Clinical pharmacology : advances and applications · 2016Review
- Review
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundThe antifungal posaconazole concentrates within host cells and protects against Aspergillus fumigatus. The specific subcellular location of posaconazole and the mechanism by which cell-associated posaconazole inhibits fungal growth remain uncharacterized.
methodsPosaconazole was conjugated with the fluorophore boron-dipyrromethene (BDP-PCZ). A549 pulmonary epithelial cells and A. fumigatus were exposed to BDP-PCZ individually and in coculture. BDP-PCZ subcellular localization and trafficking were observed using confocal microscopy and flow cytometry.
resultsBDP-PCZ concentrated within A549 cell membranes, and in particular within the endoplasmic reticulum. Epithelial cell-associated BDP-PCZ rapidly transferred to and concentrated within A. fumigatus cell membranes on contact. BDP-PCZ transfer to conidia did not require phagocytosis and was markedly enhanced by the conidial hydrophobin RodA. Within AF, BDP-PCZ also concentrated in membranes including the endoplasmic reticulum and colocalized with the azole target enzyme CYP51a. Concentration of BDP-PCZ within host and fungal cell membranes persisted for >48 hours and could be competitively inhibited by posaconazole but not voriconazole.
conclusionsPosaconazole concentrates within host cell membranes and rapidly transfers to A. fumigatus, where it accumulates to high concentrations and persists at the site of its target enzyme. These intracellular and intercellular pharmacokinetic properties probably contribute to the efficacy of PCZ.
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