Fig. 9: Virulence and micafungin susceptibility of the C. glabrata ipi1R70H mutant in vivo. | Nature Communications

Fig. 9: Virulence and micafungin susceptibility of the C. glabrata ipi1R70H mutant in vivo.

From: Mechanisms of multidrug resistance caused by an Ipi1 mutation in the fungal pathogen Candida glabrata

Fig. 9

a Susceptibility of the C. glabrata ipi1R70H mutant to macrophage killing. Logarithmic-phase cells of C. glabrata wild-type strain (CBS138) and the ipi1R70H mutant were cocultured with murine RAW 264 macrophages at 37 °C for 2 h. Percent killing is expressed as the percent reduction of CFU recovered from cocultures compared with the CFU from control cultures (C. glabrata cells without macrophages). All data obtained from the two independent experiments were compared between the wild-type and ipi1R70H strain groups (n = 14, each). The difference was not statistically significant (ns, not significant; two-tailed Mann–Whitney U test). b A mouse model of disseminated candidiasis. Immunocompetent mice were intravenously inoculated with 8 × 107 cells of either C. glabrata wild-type or ipi1R70H strain (n = 9 for the wild-type strain and n = 10 for the ipi1R70H mutant). Bilateral kidneys, spleen, and liver were excised 7 days after injection. Appropriate dilutions of organ homogenates were plated, and the numbers of CFU were counted after 2 days of incubation at 30 °C. Numbers of recovered CFU from each organ are indicated for individual mice in the scatter plots. The geometric mean is shown as a bar. ns, not significant (two-tailed Mann–Whitney U test). The representative data of two independent experiments are shown. c, d A silkworm infection model. Larvae were inoculated with 2.0–2.5 × 107 cells of each C. glabrata strain and injected with an echinocandin-class antifungal agent (micafungin, caspofungin, or anidulafungin) dissolved in saline or saline alone (50 μL). Twenty-four hours later, hemolymph was collected and spread on YPD plates to calculate CFU. The number of larvae is shown in parenthesis. Data were analyzed and presented as described above (ns, not significant; two-tailed Mann–Whitney U test). Source data for all panels are provided as a Source Data file.

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