Chiral Fluorescent Antifungal Azole Probes Detect Resistance, Uptake Dynamics, and Subcellular Distribution in Candida Species.

Autor: Koren V; School of Chemistry, Raymond and Beverley Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel., Ben-Zeev E; Ilana and Pascal Mantoux Institute for Bioinformatics and Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 7610001, Israel., Voronov I; School of Chemistry, Raymond and Beverley Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel., Fridman M; School of Chemistry, Raymond and Beverley Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
Jazyk: angličtina
Zdroj: JACS Au [JACS Au] 2024 Aug 13; Vol. 4 (8), pp. 3157-3169. Date of Electronic Publication: 2024 Aug 13 (Print Publication: 2024).
DOI: 10.1021/jacsau.4c00479
Abstrakt: Azoles are essential for fungal infection treatment, yet the increasing resistance highlights the need for innovative diagnostic tools and strategies to revitalize this class of antifungals. We developed two enantiomers of a fluorescent antifungal azole probe ( 1 S and 1 R ), analyzing 60 Candida strains via live-cell microscopy. A database of azole distribution images in strains of Candida albicans , Candida glabrata , and Candida parapsilosis , among the most important pathogenic Candida species, was established and analyzed. This analysis revealed distinct populations of yeast cells based on the correlation between fluorescent probe uptake and cell diameter. Varied uptake levels and subcellular distribution patterns were observed in C. albicans , C. glabrata , and C. parapsilosis , with the latter displaying increased localization to lipid droplets. Comparison of the more potent fluorescent antifungal azole probe enantiomer 1 S with the moderately potent enantiomer 1 R highlighted time-dependent differences in the uptake profiles. The former displayed a marked elevation in uptake after approximately 150 min, indicating the time required for significant cell permeabilization to occur and its association with the azole's antifungal activity potency. Divergent uptake levels between susceptible and high efflux-based azole-resistant strains were detected, offering a rapid diagnostic approach for identifying azole resistance. This study highlights unique insights achievable through fluorescent antifungal azole probes, unraveling the complexities of azole resistance, subcellular dynamics, and uptake within fungal pathogens.
Competing Interests: The authors declare no competing financial interest.
(© 2024 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE
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