A*STAR scientists from the Institute of Molecular and Cell Biology (IMCB) have identified what eluded yeast scientists for the past 100 years, by constructing stable haploid strains of Candida albicans, the most prevalent human fungal pathogen. This discovery, jointly made by two teams of scientists led by Prof Wang Yue of IMCB and Prof Judith Berman of the University of Minnesota, will enable scientists to effectively target and treat infections by Candida albicans. The findings, "The 'obligate diploid' Candida albicans forms mating-competent haploids", were published in the online issue of Nature on 30 January 2013.
Candida albicans ranks among the top four microbial pathogens in hospital-acquired infections of the blood, which has a mortality rate of as high as 45%. Currently, the choice of drugs for treating infections by this pathogen is limited, and drug-resistance has emerged worldwide, posing a great challenge to medicine.
Importance of the discovery
Nearly all other fungi have a haploid and a diploid phase in their life cycle, enabling the haploid cells to mate and generate genetic variations. However, up till this recent discovery, yeast scientists the world over had been unable to identify a haploid phase of this fungus.
Commenting on the significance of the discovery, Dr Mohan Balasubramanian, Senior Investigator at Temasek Lifesciences Laboratory and a leading yeast geneticist in the world, said, "The scientists show that the human pathogenic yeast Candida albicans, long thought of as always having two copies of each chromosome and no sexual reproduction in its life, in fact can and does exist as a sexually reproducing cell carrying only one copy of its genome."
Without a haploid phase, it is indeed extremely difficult for scientists to carry out genetic screens in fungi as this would require the precise targeting of both copies of a gene in a diploid organism to be able to observe a change, thus hindering the progress of the study of the virulence and delaying the development of effective treatment of fungal infections. With this discovery of the haploid phase in Candida albicans, however, scientists will now be able to easily target just one copy of the gene to observe a change, allowing for more successful screening and speeding up the discovery of targets for the development of drugs.
Prof Wang, who is a Research Director at IMCB, said, "Our discovery helps to fill a long missing gap in the life cycle of this important pathogen, greatly advancing our understanding of how it generates genetic variations for evolution and adaptation. At the same time, haploid Candida albicans also allows scientists to carry out traditional genetic screens that will certainly accelerate the identification of genes important for infection and drug targets for medical intervention."
Dr Balasubramanian said, "The paper by Wang, Berman and colleagues cuts across multiple fields, including evolutionary biology, genetics, and medical microbiology. The tools the authors have developed will help speed up the analyses of gene function in this important pathogen and might also therefore speed up our efforts to cure Candida infections".