ArticleAntimicrobial agents and chemotherapy2015
Trafficking through the late endosome significantly impacts Candida albicans tolerance of the azole antifungals.
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 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Ergosterol from Yeasts PromotesInternational journal of molecular sciences · 2026Article
- Isw2-mediated chromatin remodeling governs antifungal tolerance and heteroresistance in Candida albicans.npj antimicrobials and resistance · 2026Article
- Azoles activate type I and type II programmed cell death pathways in crop pathogenic fungi.Nature communications · 2024Article
- The Metabolism of Susceptibility: Clearing the FoG Between Tolerance and Resistance inCurrent clinical microbiology reports · 2023Article
- Targeting fungal membrane homeostasis with imidazopyrazoindoles impairs azole resistance and biofilm formation.Nature communications · 2022Article
- Molecular mechanisms underlying the emergence of polygenetic antifungal drug resistance inJAC-antimicrobial resistance · 2022Article
- Combination of Miconazole and Domiphen Bromide Is Fungicidal against Biofilms of ResistantAntimicrobial agents and chemotherapy · 2020Article
- Combining Miconazole and Domiphen Bromide Results in Excess of Reactive Oxygen Species and Killing of Biofilm Cells.Frontiers in cell and developmental biology · 2020Article
- Identification and Characterization of Mediators of Fluconazole Tolerance inFrontiers in microbiology · 2020Article
- Screening theAntimicrobial agents and chemotherapy · 2019Article
- Titrating Gene Function in the Human Fungal Pathogen Candida albicans through Poly-Adenosine Tract Insertion.mSphere · 2019Article
- Inhibition of Vesicular Transport Influences Fungal Susceptibility to Fluconazole.Antimicrobial agents and chemotherapy · 2019Article
- The Vacuolar CamSphere · 2019Article
- Eucalyptal D Enhances the Antifungal Effect of Fluconazole on Fluconazole-ResistantFrontiers in cellular and infection microbiology · 2019Article
- Loss of C-5 Sterol Desaturase Activity inAntimicrobial agents and chemotherapy · 2019Article
- Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia.Nature communications · 2018Article
- Global analysis of genetic circuitry and adaptive mechanisms enabling resistance to the azole antifungal drugs.PLoS genetics · 2018Article
- An Azole-Tolerant Endosomal Trafficking Mutant of Candida albicans Is Susceptible to Azole Treatment in a Mouse Model of Vaginal Candidiasis.Antimicrobial agents and chemotherapy · 2017Article
- Identification of small molecules that disrupt vacuolar function in the pathogen Candida albicans.PloS one · 2017Article
- Endosomal Trafficking Defects Can Induce Calcium-Dependent Azole Tolerance in Candida albicans.Antimicrobial agents and chemotherapy · 2016Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The azole antifungals block ergosterol biosynthesis by inhibiting lanosterol demethylase (Erg11p). The resulting depletion of cellular ergosterol and the accumulation of "toxic" sterol intermediates are both thought to compromise plasma membrane function. However, the effects of ergosterol depletion upon the function of intracellular membranes and organelles are not well described. The purpose of this study was to characterize the effects of azole treatment upon the integrity of the Candida albicans vacuole and to determine whether, in turn, vacuolar trafficking influences azole susceptibility. Profound fragmentation of the C. albicans vacuole can be observed as an early consequence of azole treatment, and it precedes significant growth inhibition. In addition, a C. albicans vps21Δ/Δ mutant, blocked in membrane trafficking through the late endosomal prevacuolar compartment (PVC), is able to grow significantly more than the wild type in the presence of several azole antifungals under standard susceptibility testing conditions. Furthermore, the vps21Δ/Δ mutant is able to grow despite the depletion of cellular ergosterol. This phenotype resembles an exaggerated form of "trailing growth" that has been described for some clinical isolates. In contrast, the vps21Δ/Δ mutant is hypersensitive to drugs that block alternate steps in ergosterol biosynthesis. On the basis of these results, we propose that endosomal trafficking defects may lead to the cellular "redistribution" of the sterol intermediates that accumulate following inhibition of ergosterol biosynthesis. Furthermore, the destination of these intermediates, or the precise cellular compartments in which they accumulate, may be an important determinant of their toxicity and thus ultimately antifungal efficacy.
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