Morphogenic regulator EFG1 affects the drug susceptibilities of pathogenic Candida albicans

Abstract

This study shows that the morphogenic regulator EFG1 level affects the drug susceptibilities of Candida albicans when grown on solid growth media. The Deltaefg1 mutant showed sensitivity particularly to those drugs that target ergosterol or its metabolism. Efg1p disruption showed a gene-dosage effect on drug susceptibilities and resulted in enhanced susceptibility to drugs in the homozygous mutant as compared with the wild type, heterozygous and revertant strains. The enhanced sensitivity to drugs was independent of the status of ATP-binding cassette and MFS multidrug efflux pumps of C. albicans. The Deltaefg1 mutant displayed increased membrane fluidity that coincided with the downregulation of ERG11 and upregulation of OLE1 and ERG3, leading to enhanced passive diffusion of drugs. Interestingly, Deltaefg1 mutant cells displayed enhanced levels of endogenous ROS levels. Notably, the higher levels of ROS in the Deltaefg1 mutant could be reversed by the addition of antioxidants. However, the restoration of ROS levels did not reverse the drug sensitivities of the Deltaefg1 mutant. Taken together, we, for the first time, establish a new role to EFG1 in affecting the drug susceptibilities of C. albicans cells, independent of ROS and known drug efflux mechanisms.

Transcription factor Efg1 contributes to the tolerance of Candida albicans biofilms against antifungal agents in vitro and in vivo

“…In that study, a Defg1 C. albicans mutant showed enhanced susceptibility to these drugs on agar, which was independent of multidrug efflux pumps. Moreover, the Defg1 C. albicans mutant displayed increased membrane fluidity on solid media, leading to enhanced passive diffusion of the drugs (Prasad et al, 2010). We observed a significant increase in intracellular miconazole levels in Defg1 sessile cells as compared to WT cells following miconazole treatment, explaining, at least in part, the increased miconazole sensitivity of Defg1 sessile cells.…”

“…Recently, Prasad et al (2010) demonstrated a role for Efg1 in mediating tolerance of C. albicans to azoles including fluconazole, ketoconazole and itraconazole and polyenes incuding AmB when grown on solid media. In that study, a Defg1 C. albicans mutant showed enhanced susceptibility to these drugs on agar, which was independent of multidrug efflux pumps.…”

Inactivation of genes TEC1 and EFG1 in Candida albicans influences extracellular matrix composition and biofilm morphology

“…fluconazole, ketoconazole, and itraconazole) and polyenes, including amphotericin B [43]. Moreover, a mutant Δ/Δ efg1 C. albicans strain showed higher susceptibility to these drugs, including miconazole and caspofungin [43,44]. Thus, the ASP of the ECM has a potential role in the tolerance to antifungals and biofilm structure, since it is accumulated much more in the ECM of the WT strain than in the more susceptible mutant Δ/Δ efg1.…”

“…It has been demonstrated that EFG1 intermediates tolerance of C. albicans to azoles (i.e. fluconazole, ketoconazole, and itraconazole) and polyenes, including amphotericin B [43]. Moreover, a mutant Δ/Δ efg1 C. albicans strain showed higher susceptibility to these drugs, including miconazole and caspofungin [43,44].…”

Sensitivity and lower protease activity of Candida albicans species isolated from Egyptian cancer patients after exposure to cytotoxic and/or radiotherapy treatment

“…All isolates were scraped from the media, suspended in Brain Heart broth; equal volumes of 30% sterile glycerol were added and mixed evenly using a vortex. The mixtures were then distributed into sterile Eppendorf tubes and stored at -80°C for long time preservation (Prasad et al, 2010). Identified C. albicans samples were subjected to susceptibility, biofilm formation, and protease activity assays in comparison to a standard strain of C. albicans, ATCC 60193.…”