The number of infections caused by fungal organisms has increased worldwide in the past decade. Such infections can be quite serious in immunocompromised patients such as those receiving chemotherapy, undergoing organ transplants, or infected with HIV. Unfortunately, the number of antifungal drugs available to treat these infections is limited. In this issue (Nature Biotechnology, Vol. 19, No. 3, 01 Mar 2001), however, Marianne De Backer and her colleagues have identified genes critical for growth in Candida albicans, a common opportunistic pathogen, and used the genes as potential targets in an antifungal drug screen.
Until now, it has been difficult to identify novel genes in C. albicans that would be useful as targets for antifungal drugs because conventional genetic analysis is stymied by the fungus's complicated lifecycle. But using information on the C. albicans genome sequence, De Backer's team has designed a system that can theoretically suppress any of C. albicans complement of genes and test whether those genes are essential for the pathogen's growth.
By designing synthetic nucleic acids that bind to genes identified in the C. albicans genome sequence, the Belgian team were able to suppress the expression and translation of 86 genes that had a detrimental effect on growth of the fungus. Although half of these genes are of unknown function, many are known to be essential in other organisms, suggesting the approach's success. In further experiments, the researchers then engineered C. albicans mutants in several of the "essential" genes and screened them for sensitivity to antifungal drugs. The authors suggest the approach may be adaptable to other similar pathogenic organisms.
Dr. Marianne D. De Backer
Department of Advanced Bio-Technologies
Dr. Dominique Sanglard
Institute of Microbiology
Rue de Bugnon 44
University Hospital Lausanne
(CHUV), 1011, Lausanne
(C) Nature Biotechnology press release.
Message posted by: Trevor M. D'Souza