Department of Metabolic and Structural Biology, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O.-CIMAP, Kukrail Picnic Spot Road, Lucknow - 226 015 (U.P.), India.
Curr Drug Targets. 2014 Jan;15(1):136-49. doi: 10.2174/138945011501140115112242.
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.
尽管有现代的抗真菌治疗，侵袭性真菌感染人类真菌病原体白色念珠菌的死亡率仍高达 40%。研究表明，三种最常见的人类真菌病原体（白色念珠菌、烟曲霉（导致死亡率高达 90%）和新型隐球菌（导致死亡率高达 70%））的耐药性是由于靶酶的突变或药物转运蛋白基因的高表达。人类真菌病原体的耐药性导致迫切需要鉴定对真菌病原体特有的新靶标。在本研究中，我们使用比较基因组学方法来寻找白色念珠菌（一种机会性真菌，可导致免疫功能低下的人类严重感染）特有的潜在靶蛋白。有趣的是，许多现有抗真菌药物的靶蛋白在人类细胞中都有同源物。为了鉴定独特的蛋白质，我们比较了白色念珠菌[SC5314]的蛋白质组，即从美国 NCBI 的 RefSeq 数据库中检索到的 14633 种总蛋白质，与人类和非致病性酵母酿酒酵母的蛋白质组进行了比较。结果表明，与人类和酿酒酵母蛋白质组相比，有 4568 种蛋白质被鉴定为白色念珠菌特有的蛋白质，而当这些独特的蛋白质与酿酒酵母蛋白质组进行比较时，最终有 2161 种蛋白质被鉴定为独特的蛋白质，去除重复后共选择了 1618 种独特的蛋白质（42 种功能已知、1566 种假设和 10 种未知）作为白色念珠菌特有的潜在抗真菌药物靶标。
