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Monday 23 October 2006

Transcriptional Profiles of the Response to Ketoconazole and Amphotericin B in Trichophyton rubrum.

By: Yu L, Zhang W, Wang L, Yang J, Liu T, Peng J, Leng W, Chen L, Li R, Jin Q.

Antimicrob Agents Chemother 2006 Oct 23; [Epub ahead of print]

Trichophyton rubrum (T. rubrum) is a pathogenic filamentous fungus of increasing medical concern. Two antifungal agents, ketoconazole (KTC) and amphotericin B (AMB), have specific activity against dermatophytes. To identify the mechanisms of action of KTC and AMB against T. rubrum, a cDNA microarray was constructed from the expressed sequence tags (ESTs) of the cDNA library from different developmental stages, and transcriptional profiles of the responses to KTC and AMB were determined. T. rubrum was exposed to sub-inhibitory concentrations of KTC and AMB for 12 hours, and microarray analysis was used to examine gene transcription. KTC exposure induced transcription of genes involved in lipid, fatty acid, and sterol metabolism, including ERG11, ERG3, ERG25, ERG6, ERG26, ERG24, ERG4, CPO, INO1, DW700960, CPR, DW696584, DW406350, and ATG15. KTC also increased transcription of the multidrug resistance gene ABC1. AMB exposure increased transcription of genes involved in lipid, fatty acid, and sterol metabolism (DW696584, EB801458, IVD, DW694010, DW688343, DW684992), membrane transport (Git1, DW706156, DW684040, DMT, DW406136, CCH1, DW710650) and stress-related responses (HSP70, HSP104, GSS, AOX, EB801455, EB801702, TDH1, UBI4), but reduced transcription of genes involved in maintenance of cell-wall integrity and signal transduction pathways (FKS1, SUN4, DW699324, GAS1, DW681613, SPS1, DW703091, STE7, DW703091, DW695308) and some ribosomal proteins. This is the first report of the use of microarray analysis to determine the effects of drug action in T. rubrum.

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