Cited by 38Lipid Membrane Structure and BehaviorAntifungal resistance and susceptibilitySpectroscopy Techniques in Biomedical and Chemical Research

The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.

Imaging of human cells exposed to an antifungal antibiotic amphotericin B reveals the mechanisms associated with the drug toxicity and cell defence

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Grela, Ewa, Piet, Mateusz, Luchowski, Rafal, Grudzinski, Wojciech, Paduch, Roman, Gruszecki, Wieslaw I.·2018·Scientific Reports

Abstract

Amphotericin B is an antibiotic used in pharmacotherapy of life-threatening mycotic infections. Unfortunately, the applicability of this antibiotic is associated with highly toxic side effects. In order to understand molecular mechanisms underlying toxicity of amphotericin B to patients, two cell lines, human normal colon epithelial cells (CCD 841 CoTr) and human colon adenocarcinoma cells (HT-29) were cultured in the presence of the drug and imaged with the application of fluorescence lifetime imaging microscopy and Raman scattering microscopy. The results of the cell viability assays confirm high toxicity of amphotericin B towards human cells. The images recorded demonstrate effective binding of amphotericin B to biomembranes. Analysis of the images reveals the operation of a defence mechanism based upon the elimination of molecules of the drug from living cells via formation of small amphotericin B-containing lipid vesicles. The fact that exosomes formed are devoid of cholesterol, as concluded on the basis of the results of Raman analysis, suggests that sequestration of sterols from the lipid phase of biomembranes is not a sole mechanism responsible for the toxic side effects of amphotericin B. Alternatively, the results imply that molecules of the drug present directly within the hydrophobic membrane core disturb the lipid membrane structure and affect their biological functions.

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  1. Casadevall, A. Emerging fungal pathogens—past, present, and future. in Public workshop, “Fungal Diseases: An Emerging Challenge to Human, Animal and Plant Health” Forum on Microbial Threats (Institute of Medicine, Washington, D.C., 2010).

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Metadata

Authors
Grela, E., Piet, M., Luchowski, R., Grudzinski, W., Paduch, R., & Gruszecki, W. I.
Affiliations
  • Maria Curie-Skłodowska University (PL)
  • Medical University of Lublin (PL)
Venue
Scientific Reports
Published
2018-09-14
Volume
8
Issue
1
Pages
14067-14067
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2890319039
Cited by
38
References
21
Citations by year
2026: 3 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 9 · 2020: 7 · 2019: 7
FWCI
2.05
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Narodowe Centrum Nauki (2015/19/B/NZ7/02159)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Spectroscopy Techniques in Biomedical and Chemical Research
Keywords
amphotericin B, drug toxicity, antifungal antibiotics, cell membrane binding, exosomes, lipid vesicles, cholesterol sequestration, membrane sterols, membrane structure, colonic epithelial cells, colon adenocarcinoma cells, fluorescence lifetime imaging
MeSH terms
Amphotericin B, Anti-Bacterial Agents, Antifungal Agents, Cell Survival, Humans, Microscopy, Fluorescence, Spectrum Analysis, Raman, HT29 Cells

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