PubMed · 4881130
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M L Littman, J E Walter. 1968. Cryptococcosis: current status.. https://doi.org/10.1016/0002-9343(68)90190-3
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Clinical isolates of Candida auris show a high prevalence of resistance to Amphotericin B (AmB)-an uncommon trait in most Candida species. Alterations in ergosterol biosynthesis can contribute to acquired AmB resistance in C. auris laboratory strains but are rarely seen in clinical isolates. In this study, we experimentally evolved two drug-susceptible Clade II isolates of C. auris to develop AmB resistance. The evolved strains displayed a four to eight fold increase in MIC50 compared to the parental cells. We analyzed changes in their karyotype, genome, lipidome, and transcriptome associated with this acquired resistance. In one lineage, AOX2 was upregulated, and its deletion reversed the AmB resistance phenotype. The aox2Δ mutant also failed to evolve AmB resistance under experimental conditions. In the same lineage, restoring the UPC2 S332R and RTG3 S101T mutations to the wild-type allele restored AmB susceptibility. In another lineage, the ergosterol and sphingolipid pathways were observed to play a critical role, and upregulation of the ERG genes elevated the total sterol content, while significant downregulation of HSX11 (glucosylceramide synthase) resulted in lower levels of glucosylceramides. To our knowledge, this study is the first to show that AmB resistance in C. auris can be acquired through mechanisms both dependent on or independent of sterol content modulation, highlighting Aox2 and Upc2 as key regulators of amphotericin resistance.
The UV-visible results of this kinetic study show that amphothericin B as Fungizone is a much stronger oxidant than CuSO(4), itself a powerful oxidant of low-density lipoprotein (LDL). Amphotericin B as AmBisome alone has no oxidizing effect on LDL while a mixture of both AmBisome and CuSO(4) induces an important potentialization of the LDL oxidation. These results allow us to believe that the high toxicity of amphotericin B is related to its capacity to modify and to weaken the structure of LDL. In addition, differential scanning calorimetry experiments show that the oxidative modifications of LDL by CuSO(4) or by amphotericin B proceed through different mechanisms.
BACKGROUND: Malignant otitis externa caused by fungal infections is rare. A review of the literature showed only 9 cases, and the causative fungus in all cases was Aspergillus. This article reports an unusual case caused by Malassezia sympodialis. METHODS: A 53-year-old man with non-insulin dependent diabetes presented with malignant otitis externa. He deteriorated despite treatment with intravenous antipseudomonal therapy and surgical debridement. Microbiologic tests revealed M. sympodialis. He responded rapidly to intravenous amphotericin. RESULTS: Systemic human infections caused by M. sympodialis have not been reported. M. furfur systemic infection is rare and has been associated lipid hyperalimentation by means of a central catheter. Only 1 other case of M. fungemia without these associated risk factors has been reported. CONCLUSIONS: The first case of malignant otitis externa caused by M. sympodialis is presented. It highlights the difficulty of initial biologic diagnosis and the need for lipid-enriched media to grow this fastidious organism.