Table 4.
C. elegans model demonstrating alternative inhibition mechanisms against Candida species.
| Candida spp. | C. elegans host | Effective antifungal agent | Effective concentrations (µg/ml) | Effect | Reference | |
|---|---|---|---|---|---|---|
| C. albicans | N2 Bristol CF512 fer-15; fem-1 adult worms | 7-Benzyloxyindole | 0.05 mM | 7-Benzyloxyindole gave nematode survival rate of >40% while the positive control (fluZ) gave >60% by Day 4, both showed significant (p < 0.05) increase of survival rates compared with the untreated control (8%). 7-Benzyloxyindole at 0.1 mM showed mild toxicity on worms with 22% survival rate compared with 55% survival by fluZ. 7-Benzyloxyindole protected infected worms by preventing hyphal filamentation through downregulation of important hyphae-specific and biofilm-related genes | Manoharan et al. (2018) | |
| C. albicans | glp-4; sek-1 young adult worms | Enterococcus faecalis bacteriocin (EntV) | 0.1 nM | Synthetic EntV (sEntV68) completely abrogated the virulence of C. albicans in infected worms, giving them lifespan similar to control worms fed with nematode food E. coli OP50. sEntV68 had no effect on the viability of C. albicans but protected the nematode by preventing hyphal morphogenesis. | Graham et al. (2017) | |
| C. albicans | fer-15; fem-1 adult worms | Cascarilla bark oil, α-longipinene, and linalool | ≥0.001% | Separate treatments with cascarilla bark oil, α-longipinene, and linalool resulted in a significant (p < 0.05) increase in survival rate (>90%) of infected nematodes just like fluZ treatment (all at 0.01%) compared with the negative control (<5%) by Day 4. These antifungal compounds only became toxic at >0.5% (v/v) to the worms. Cascarilla bark oil, α-longipinene, and linalool protected infected worms by preventing hyphal filamentation but no direct effect on C. albicans planktonic cells | Manoharan et al. (2017c) | |
| C. albicans | glp-4; sek-1 adult worms | Loureirin A (Lou A) | 40 | Lou A significantly (p < 0.05) protected infected nematodes compared with the DMSO control in 144 h. More so, Lou A did not display any cytotoxic activity against the worms at 160 µg/ml. At effective in vivo concentration of 40 µg/ml, Lou A did not inhibit the growth of C. albicans but suppressed virulence trait such as adhesion, colonization, and hyphal filamentation | Lin et al. (2019) | |
| C. albicans | N2 young adult worms | Piperine | ≥BIC (32) | Piperine treatment helped worms to combat infection in a dose-dependent manner leading to a significant (p < 0.05) reduction in C. albicans load. Piperine did not result in cytotoxity at sub-BIC, BIC, and 2 × BIC in worms. Piperine in vivo efficacy was mainly through hindering C. albicans colonization in nematode intestine by downregulating some important hyphae-specific genes but not affecting the growth and metabolism of the pathogen | Priya and Pandian (2020) | |
| C. albicans, C. glabrata, and C. tropicalis | L4 worms | Quinic acid and undecanoic acid (QA-UDA) | BIC a (100) | QA-UDA at BIC increased the survival rates of worms infected by C. albicans, C. glabrata, and C. tropicalis to 216, 384, and 348 h compared with 156, 180, and 252 h of untreated infected worms, respectively. QA-UDA reduced in vivo biofilm formation and colonization of yeast pathogens in worms | Muthamil et al. (2018) | |
| C. albicans | fer-15; fem-1 adult worms | Camphor and fenchyl alcohol | 0.01% | Treatment of infected worms with camphor and fenchyl alcohol significantly (p < 0.05) increased the survival rates of infected worms to >70% and >50%, respectively, compared with 5% untreated control. These compounds had no effect on worm survival and viability at concentrations of 0.05% and 0.1% in 4 days, but they became significantly toxic (p < 0.05) at 0.5%. Camphor and fenchyl alcohol at BIC (approximately 50 times the MIC) had effect on C. albicans biofilm and hyphal filamentation but not on the planktonic cells | Manoharan et al. (2017b) | |
| C. albicans | L4 worms | 5-Hydroxymethyl-2-furaldehyde (5HM2F) | MBIC (400) | Increased survival time of infected worms when treated with 5HM2F (120 h) compared with 96 h of control group. 5HM2F displayed no cytotoxic effect on worms by120 h. 5HM2F below 500 µg/ml does not have antifungal effect on C. albicans except on some virulence factors such as biofilm formation, morphological transition, and production of secreted hydrolases | Subramenium et al. (2017) | |
a
BICs for C. albicans, C. glabrata, and C. tropicalis in combination with QA/UDA were 100/5, 100/10, and 200/20 µg/ml, respectively. BIC, biofilm inhibition concentration; MBIC, minimum biofilm inhibitory concentration.