Open AccessMorphogenic regulator EFG1 affects the drug susceptibilities of pathogenic Candida albicans
Author(s) -
Prasad Tulika,
Hameed Saif,
Manoharlal Raman,
Biswas Sudipta,
Mukhopadhyay Chinmay K.,
Goswami Shyamal K.,
Prasad Rajendra
Publication year - 2010
Publication title -
fems yeast research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.991
H-Index - 92
eISSN - 1567-1364
pISSN - 1567-1356
DOI - 10.1111/j.1567-1364.2010.00639.x
Subject(s) - candida albicans , mutant , efflux , biology , downregulation and upregulation , regulator , ergosterol , corpus albicans , drug , microbiology and biotechnology , pharmacology , biochemistry , gene
This study shows that the morphogenic regulator EFG1 level affects the drug susceptibilities of Candida albicans when grown on solid growth media. The Δ efg1 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 Δ efg1 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, Δ efg1 mutant cells displayed enhanced levels of endogenous ROS levels. Notably, the higher levels of ROS in the Δ efg1 mutant could be reversed by the addition of antioxidants. However, the restoration of ROS levels did not reverse the drug sensitivities of the Δ efg1 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.