Fig. 1: Intracellular C. glabrata (ICG) cells show multiple characteristics of persisters. | Nature Communications

Fig. 1: Intracellular C. glabrata (ICG) cells show multiple characteristics of persisters.

From: Macrophage internalization creates a multidrug-tolerant fungal persister reservoir and facilitates the emergence of drug resistance

Fig. 1

a ICG are less sensitive to micafungin (0.03 µg/ml), AMB (1 µg/ml), fluconazole (8 µg/ml), and voriconazole (0.06 µg/ml) than their planktonic counterparts. n = 4 biological replicates over two independent experiments. b ICG survival was higher than that of planktonic cells over a range of micafungin concentrations. n = 4 biological replicates over two independent experiments. c ICG exposed to 8X MIC of micafungin (0.125 µg/ml) or AMB (4 µg/ml) show a biphasic killing pattern. n = 3 biological replicates over 3 independent experiments. d Proportions of daughter (AF647 ConA-positive) and mother cells (FITC- and AF-647 ConA-positive) in micafungin-treated ICG remain stable over the course of treatment, indicating a lack of proliferation, whereas untreated ICG show a marked increase in the proportion of daughter cells. n = 3 biological replicates in a single experiment. e Propidium iodide (PI)-negative C. glabrata cells released from micafungin-treated macrophages have lower culturability, as assessed by colony forming units (CFU), than PI-negative C. glabrata released from untreated macrophages. n = 4–6 biological replicates over two independent experiments. f PI-negative C. glabrata released from micafungin-treated macrophages are capable of reinfecting new macrophages, albeit at a lower rate relative to untreated counterparts. n = 4–5 biological replicates over two independent experiments. g Micafungin penetrated macrophages and accumulated there at a high concentration, similar to clofazimine and higher than moxifloxacin and rifampicin. n = 3 biological replicates in a single experiment. PI propidium iodide, AF-647 ConA Alexa Flour 647-conjugated concanavalin A, FITC fluorescein isothiocyanate, ICG intracellular C. glabrata, MCF micafungin AMB amphotericin B, MIC minimum inhibitory concentration, CFU colony forming units, LC-MS/MS liquid chromatography-tandem mass spectrometry. Data are presented as mean values +/− standard deviations.

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