Candida albicans infection is a significant complication in the treatment of immunocompromized patients. Novel treatment strategies have included targeting fungal pathogen RNA with antisense oligonucleotides. A number of promising compounds have been identified, but little has been known about the mechanisms of oligonucleotide uptake into fungi. In the January 29 early edition of Proceedings of the National Academy of Sciences, Matthew D. Disney and colleagues at the University of Rochester, New York, USA, show that oligonucleotides can accumulate in C. albicans and inhibit its growth (PNAS, DOI:10.1073/pnas.0337462100, January 27, 2003).

Disney et al. grew C. albicans cultures in the presence or absence of oligonucleotides. They observed that oligonucleotides were taken up from cell culture medium in an energy-dependent manner, producing higher intracellular concentrations than the concentrations in the media or in mammalian cells. In addition, they describe an oligonucleotide that mimics a ribosomal RNA (rRNA) hairpin which inhibited growth of a C. albicans strain below pH 4.0. In vivo dimethyl sulfate (DMS) modification of rRNA and rates of protein synthesis showed that the inhibitory effect was due to targeting of the ribosome.

"Taken together, these results suggest that C. albicans infections may be particularly susceptible to oligonucleotide-based therapeutics," conclude the authors.