Title:Genomic Identification of Potential Targets Unique to Candida albicans for the Discovery of Antifungal Agents
Volume: 15
Issue: 1
Author(s): Himanshu Tripathi, Suaib Luqman, Abha Meena and Feroz Khan
Affiliation:
Keywords:
Antifungal agents, Candida albicans, drugs, comparative genomics, proteome, targets.
Abstract: Despite of modern antifungal therapy, the mortality rates of invasive infection with human fungal pathogen
Candida albicans are up to 40%. Studies suggest that drug resistance in the three most common species of human fungal
pathogens viz., C. albicans, Aspergillus fumigatus (causing mortality rate up to 90%) and Cryptococcus neoformans (causing
mortality rate up to 70%) is due to mutations in the target enzymes or high expression of drug transporter genes. Drug
resistance in human fungal pathogens has led to an imperative need for the identification of new targets unique to fungal
pathogens. In the present study, we have used a comparative genomics approach to find out potential target proteins
unique to C. albicans, an opportunistic fungus responsible for severe infection in immune-compromised human. Interestingly,
many target proteins of existing antifungal agents showed orthologs in human cells. To identify unique proteins, we
have compared proteome of C. albicans [SC5314] i.e., 14,633 total proteins retrieved from the RefSeq database of NCBI,
USA with proteome of human and non-pathogenic yeast Saccharomyces cerevisiae. Results showed that 4,568 proteins
were identified unique to C. albicans as compared to those of human and later when these unique proteins were compared
with S. cerevisiae proteome, finally 2,161 proteins were identified as unique proteins and after removing repeats total
1,618 unique proteins (42 functionally known, 1,566 hypothetical and 10 unknown) were selected as potential antifungal
drug targets unique to C. albicans.