Table 3.
Evaluation of effective agents against drug-resistant Candida species in a C. elegans model.
| Candida spp. | C. elegans host | Kind of drug resistance and MIC | Antifungal compound/agent | Time of preinfection (min) | Effect | Reference |
|---|---|---|---|---|---|---|
| C. albicans | AU37 L4 worms | fluZ | 2-(5,7-Dibromoquinolin-8-yl)oxy)-N′-(4-nitrobenzylidene) acetohydrazide (4b) | 90 | Compound 4b exhibited broad-spectrum antifungal activity towards species pf Candida, Cryptococcus, and Aspergillus at a concentration of 0.5 µg/ml, as well as enhanced survival of C. elegans infected with fluz-resistant C. albicans. This compound targets metal ion homeostasis | Elghazawy et al. (2017) and Mohammad et al. (2018) |
| C. albicans | N2 worms | fluZ 256 µg/ml | Caffeic acid phenethyl ester (CAPE) and fluZ | 120 | CAPE plus fluZ synergistically increased the survival rate of infected worms significantly compared with single treatment with either CAPE or fluZ. CAPE plus fluZ also significantly (p < 0.01) reduced C. albicans burden in nematode intestines compared with just CAPE, fluZ, or the untreated control (all at 2 µg/ml) | Sun et al. (2018) |
| C. albicans and C. auris | AU37 L4 worms | fluZ >64 µg/ml | Phenylthiazole small molecule (compound 1) | 90 | Compound 1 (at 5 and 10 µg/ml) enhanced the survival of C. albicans-infected nematodes, giving >70% survival rate (just like 5 µg/ml of 5-fluorocytosine control) by Day 3 postinfection compared with 0% of untreated infected worms. Similarly, Compound 1 (at 10 µg/ml) prolonged C. auris-infected worms giving ~70% survival by Day 4 compared with 0% of untreated infected worms | Mohammad et al. (2019) |
| C. albicans | glp-4; sek-1 worms | fluZ >128 µg/ml | Pyridoxatin (PYR) | 120 | PYR rescued and prolonged infected nematodes in a dose-dependent manner with 4 µg/ml giving ~50% survival rate after 5 days of treatment | Chang et al. (2015) |
| C. albicans | AU37 L4 worms | fluZ >64 µg/ml; itraconazole (itZ) and voZ >16 µg/ml | Sulfa drugsa + fluZ | 180 | Sulfa (10 × MICb) and fluZ (10 µg/ml) combinations gave a significant (p < 0.05) reduction of C. albicans burden in infected worms (which is comparable with 5-fluorocytosine control) after 24 h treatment compared with fluZ and the DMSO-untreated controls. There was no significant difference among the activities of the 4 sulfa with fluZ combinations | Eldesouky et al. (2018b) |
| C. auris | AU37 L4 worms | Azole resistant; fluZ >128 µg/ml; voZ = 16 µg/ml; itZ = 2 µg/ml | Sulfamethoxazole + voZ | 30 | The combination of sulfamethoxazole (128 µg/ml) with voZ (0.5 µg/ml) prolonged the life of infected worms by ~70% as against only sulfamethoxazole, voZ, or untreated control which could not keep worms alive till Day 5 | Eldesouky et al. (2018a) |
MIC, minimum inhibition concentration. aSulfamethoxazole (SMX), sulfadoxine (SDX), sulfadimethoxine (SDM), or sulfamethoxypyridazine (SMP). bMICs of SMX, SDX, and SMP = 512 µg/ml, while MIC of SDM = 1,024 µg/ml.