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Antimicrobial Agents and Chemotherapy, January 2007, p. 144-153, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00755-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Transcriptional Profiles of the Response to Ketoconazole and Amphotericin B in Trichophyton rubrum{triangledown} ,{dagger}

Lu Yu,1,{ddagger} Wenliang Zhang,1,3,5,{ddagger} Lingling Wang,1 Jian Yang,1 Tao Liu,1 Junping Peng,1 Wenchuan Leng,1 Lihong Chen,1 Ruoyu Li,4 and Qi Jin1,2*

State Key Laboratory for Molecular Virology and Genetic Engineering, Chinese Center for Disease Control and Prevention, Beijing 100176, China,1 Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing 100730, China,2 College of Biological Sciences, China Agricultural University, Beijing 100094, China,3 Research Centre for Medical Mycology, Beijing 100034, China,4 State Key Laboratories for Agrobiotechnology, China Agricultural University, Beijing 100094, China5

Received 22 June 2006/ Returned for modification 31 July 2006/ Accepted 15 October 2006

Trichophyton 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 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 subinhibitory concentrations of KTC and AMB for 12 h, 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.

* Corresponding author. Mailing address: State Key Laboratory for Molecular Virology and Genetic Engineering, Chinese Center for Disease Control and Prevention, Beijing 100176, China. Phone: 86 10 67876915. Fax: 86 10 67877736. E-mail: zdsys{at}vip.sina.com.

{triangledown} Published ahead of print on 23 October, 2006.

{dagger} Supplemental material for this article may be found at http://aac.asm.org/.

{ddagger} Both authors contributed equally to this work.

Antimicrobial Agents and Chemotherapy, January 2007, p. 144-153, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00755-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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