Fig 12.

Impact of drug combinations on Galleria mellonella survival during systemic fungal infection. (A) Larvae of G. mellonella were systemically infected with Candida albicans isolates (3 × 10⁵ cells per larva) and subsequently treated with either no drug (DMSO as vehicle), fluconazole (FLC, 20 µg/mL), sortin2 (50 µM), 1,4-benzodiazepines (1,4-BZDs) (PA158 or PA162, 50 µM), or a combination of FLC (20 µg/mL) and 1,4-BZDs (50 µM) in volumes of 10 µL/larva. Additional control groups of larvae were systemically injected with PBS and treated with either DMSO, FLC, sortin2, or 1,4-BZDs in the absence of fungal infection (B). Survival of larvae infected with SC5314 (C), SP-945 (D), or P60002 (E) was monitored daily for 10 days for three to five groups of larvae with 12 larvae per group for each condition (n = 36–60 larvae per group). Asterisks indicate significant differences for comparisons between FLC and drug combinations (FLC vs FLC + sortin2, FLC vs FLC + PA158, FLC vs FLC + PA162), colored according to the corresponding lines, based on Log-rank (Mantel–Cox) tests. All statistical comparisons between each two groups are included in Table S1E. (F-H) Fungal burdens from larvae treated with single agents or drug combinations recovered before or at 4 days post infection (n = 12 larvae/group). Gray dots show larvae that had succumbed to infection before or at 4 days, white dots show larvae sacrificed on day 4. Error bars represent ± SEM, asterisks indicate significant differences based on unpaired t-tests, * P < 0.05; ** P < 0.01.