Amphotericin B: current understanding of mechanisms of action

Brajtburg, J; Powderly, William G.; Kobayashi, George S.; Medoff, Gerald

doi:10.1128/aac.34.2.183

Cited by 479 publications

(281 citation statements)

References 59 publications

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“…1) is a life saving polyene antibiotic used to treat deep-seated mycotic infections [1,2]. Despite very strong side effects and toxicity to patients AmB is constantly being applied owing to its pharmaceutical effectiveness [3]. Severe mycotic infections accompanying AIDS are frequently treated with AmB formulations.…”

Section: Introductionmentioning

confidence: 99%

Molecular organization of antifungal antibiotic amphotericin B in lipid monolayers studied by means of Fluorescence Lifetime Imaging Microscopy

Gruszecki

Luchowski

Gagoś

et al. 2009

Biophysical Chemistry

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Amphotericin B (AmB) is a life-saving polyene antibiotic used to treat deep-seated mycotic infections. Both the mode of therapeutic action as well as toxic side effects are directly dependent on molecular organization of the drug. Binding of AmB to lipid monolayers formed with dipalmitoylphosphatidylcholine, pure and containing 40 mol% cholesterol or ergosterol, the sterols of human and fungi respectively, has been examined by means of

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Section: Introductionmentioning

confidence: 99%

Molecular organization of antifungal antibiotic amphotericin B in lipid monolayers studied by means of Fluorescence Lifetime Imaging Microscopy

Gruszecki

Luchowski

Gagoś

et al. 2009

Biophysical Chemistry

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“…The polyene antifungals, such as nystatin and amphotericin B, function by binding to membrane ergosterol and inducing cellular leakage, resulting in cell death. 30 Other groups of antifungals, including the allylamines, 217 morpholines 15 and azoles, 279 inhibit specific steps in ergosterol biosynthesis and will be discussed in more detail later in this review. All of these compounds have limitations as to their application to human infection or have seen the appearance of significant levels of resistance in several pathogenic fungi.…”

Section: Sterolsmentioning

confidence: 99%

Biochemistry, cell biology and molecular biology of lipids ofSaccharomyces cerevisiae

Daum

Lees

Bard

et al. 1998

Yeast

580

380

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The yeast Saccharomyces cerevisiae is a powerful experimental system to study biochemical, cell biological and molecular biological aspects of lipid synthesis. Most but not all genes encoding enzymes involved in fatty acid, phospholipid, sterol or sphingolipid biosynthesis of this unicellular eukaryote have been cloned, and many gene products have been functionally characterized. Less information is available about genes and gene products governing the transport of lipids between organelles and within membranes, turnover and degradation of complex lipids, regulation of lipid biosynthesis, and linkage of lipid metabolism to other cellular processes. Here we summarize current knowledge about lipid biosynthetic pathways in S. cerevisiae and describe the characteristic features of the gene products involved. We focus on recent discoveries in these fields and address questions on the regulation of lipid synthesis, subcellular localization of lipid biosynthetic steps, cross‐talk between organelles during lipid synthesis and subcellular distribution of lipids. Finally, we discuss distinct functions of certain key lipids and their possible roles in cellular processes. © 1998 John Wiley & Sons, Ltd.

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“…6 Oxidative stress induction is considered to be another AmB-induced toxic event in the cells of this pathogenic fungus. 2,7 In our recent study, we observed vacuole membrane fragmentation in Saccharomyces cerevisiae cells on incubation with AmB in distilled water, in which the organelle actively functions for cellular ion homeostasis and osmoregulation. 8 In addition to the alteration in plasma membrane permeability in S. cerevisiae, AmB lethality could be attributed, at least in part, to its direct disruptive action on vacuoles.…”

Section: Introductionmentioning

confidence: 99%

“…1 Medical treatment for candidiasis includes chemotherapy using amphotericin B (AmB; Figure 1), a typical polyene macrolide antibiotic that is derived from the actinomycete Streptomyces nodosus. 2,3 AmB binds to ergosterol in the fungal plasma membrane and induces lethal damage by altering plasma membrane permeability. 4 However, the AmB-induced lethal damage cannot be simply explained by the disturbance in plasma membrane ion transfer function because the leakage of K + results in various secondary effects, including the inhibition of protein synthesis.…”

Section: Introductionmentioning

confidence: 99%

The vacuole-targeting fungicidal activity of amphotericin B against the pathogenic fungus Candida albicans and its enhancement by allicin

et al. 2009

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In this study, the vacuole disruptive activity was evaluated as a cause of amphotericin B (AmB) lethality against the pathogenic fungus Candida albicans in terms of its enhancement by allicin, an allyl-sulfur compound from garlic. Vacuole disruption was observed in parallel to AmB-induced cell death when the antibiotic was used at a lethal concentration and at a non-lethal concentration in combination with allicin. Allicin did not enhance AmB-induced cell death and the accompanying vacuole disruption when the cells were incubated with exogenous ergosterol for its enrichment in the vacuole. The vacuoles isolated from intact cells could be directly disrupted by the action of AmB to the same extent in the absence and presence of allicin, whereas the organelles isolated from ergosterol-enriched cells were resistant to its direct disruptive action. AmB was similarly incorporated into the fungal cytoplasm in cells with or without ergosterol enrichment, supporting the fact that AmB-induced vacuole disruption depends on its direct disruptive action on the organelle. In agreement with these findings, allicin was found to inhibit ergosterol transport from the plasma membrane to the cytoplasm, which is considered to be a cellular protective response to AmB-induced vacuole disruption in S. cerevisiae. Our study suggests that AmB lethality against C. albicans depends at least in part on its vacuole disruptive activity under the physiological condition permissive for invasive growth of the fungus.

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Amphotericin B: current understanding of mechanisms of action

Cited by 479 publications

References 59 publications

Molecular organization of antifungal antibiotic amphotericin B in lipid monolayers studied by means of Fluorescence Lifetime Imaging Microscopy

Molecular organization of antifungal antibiotic amphotericin B in lipid monolayers studied by means of Fluorescence Lifetime Imaging Microscopy

Biochemistry, cell biology and molecular biology of lipids ofSaccharomyces cerevisiae

The vacuole-targeting fungicidal activity of amphotericin B against the pathogenic fungus Candida albicans and its enhancement by allicin

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