Group I intron renders differential susceptibility of Candida albicans to Bleomycin.
The alarming increase in drug resistance gained by fungal pathogens has raised an urgent need to develop drugs against novel targets. Candida albicans, an opportunistic fungal pathogen, harbors in its 25S rRNA gene, a self-splicing Group I intron, which can act as a selective drug target. We report that Bleomycin selectively inhibits the self-splicing of Group I intron of C. albicans at IC(50) = 1.2 microM, leading to accumulation of precursor RNA as evinced by Reverse Transcriptase PCR. Drug susceptibility assays including MIC determination, growth curve analysis and disc diffusion assays indicate a strong susceptibility of the intron-containing strain (4-1) than the intronless strain (62-1). These results on the preferential targeting of Group I intron of C. albicans by Bleomycin might form a basis for design of small molecules that inhibit self-splicing of RNA as a antimicrobial tool against life-threatening microorganisms.
Jayaguru
Prathiba
P
Department of Genetics, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600 113, India.
Raghunathan
Malathi
M
D000935:Antifungal Agents / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics*; D025141:Drug Resistance, Fungal / Q000235:genetics*; D007438:Introns; D008826:Microbial Sensitivity Tests; D012322:RNA Precursors / Q000378:metabolism; D012326:RNA Splicing / Q000502:physiology*; D016337:RNA, Catalytic / Q000502:physiology; D012331:RNA, Fungal / Q000302:isolation & purification / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000935:Antifungal Agents; D012322:RNA Precursors; D016337:RNA, Catalytic; D012331:RNA, Fungal; D001761:Bleomycin