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Target genes for antifungal drugs
By Bijal P. Trivedi

Scientists in Belgium have developed a genome-wide screen for finding genes important for the growth of the pathogenic fungus, Candida albicans. In recent decades, physicians have observed an increase in the variety and number of fungal infections, especially among individuals with weak immune systems—chemotherapy patients, organ transplant recipients, and those infected with HIV. Currently there are few antifungal drugs and those that exist are toxic. In addition, drug resistant fungal strains have emerged. Hence the need to identify new drug targets, like critical growth genes.

Candida albicans

Marianne De Backer, of Janssen Pharmaceutica in Beerse, Belgium, and colleagues essentially blocked the activity of individual genes, and looked for cells that had trouble growing. Disrupting certain genes slowed but did not stop the growth of cells.

The study involved screening two thousand modified C. albicans cells, each of which was 'missing' a different gene. The researchers identified 86 genes that are critical for growth. Of these the function of 45 genes is completely unknown, and 33 genes had no counterparts in other species.

Having identified critical growth genes, De Backer's team used the information to create 'crippled' strains of C. albicans that they are using for screening antifungal compounds.

"The work of De Backer et al. is a nice example of how genome information, intelligent design of molecular tools, and conventional drug screening on the relevant yeast pathogen can be combined," writes Dominique Sanglard, of the University Hospital Lausanne, Switzerland, in an accompanying article.

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De Backer, M. D. et al. An antisense-based functional genomics approach for identification of genes critical for growth of Candida albicans. Nat Biotechnol 19, 235-241 (March 2001).
Sanglard, D. Integrated antifungal drug discovery in Candida albicans. Nat Biotechnol. 19, 212-213 (March 2001).

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