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A genome-wide steroid response study of the major human fungal pathogen Candida albicans

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Abstract

In the absence of steroid receptors and any known mechanism of gene regulation by steroid hormones in Candida albicans, we did a genome-wide analysis of C. albicans cells treated with progesterone using Eurogentec cDNA microarrays to find the complete repertoire of steroid responsive genes. Northern blotting analysis was employed to validate the genes that were differentially regulated by progesterone in the microarray experiments. A total of 99 genes were found to be significantly regulated by progesterone, among them 60 were up-regulated and 39 were down-regulated. It was observed that progesterone considerably enhanced the expression of multi-drug resistance (MDR) genes belonging to ATP Binding Cassette (CDR1 and CDR2) super-family of multidrug transporters, suggesting a possible relationship between steroid stress and MDR genes. Several genes associated with hyphal induction and the establishment of pathogenesis were also found up-regulated. In silico search for various transcription factor (TF) binding sites in the promoter of the affected genes revealed that EFG1, CPH1, NRG1, TUP1, MIG1 and AP-1 regulated genes are responsive to progesterone. The stress responsive elements (STRE; AG4 or C4T) were also found in the promoters of several responsive genes. Our data sheds new light on the regulation of gene expression in C. albicans by human steroids, and its correlation with drug resistance, virulence, morphogenesis and general stress response. A comparison with drug induced stress response has also been discussed.

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Acknowledgements

The work presented in this paper has been supported in part by grants to R.P. from Indo-French Centre for the Promotion of Advanced Research (IFCPAR Project No. 3403-2), Department of Biotechnology, India (BT/PR3825/MED/14/488(a)/2003) and (BT/PR4862/BRB/10/360/2004). D.B. and S.S. thank the Council of Scientific and Industrial Research (CSIR) and the University Grants Commission (UGC) respectively, for the award of Senior Research Fellowships. N.M. was supported by a fellowship from CSIC through the I3P-BPG2004 programme. Useful help in this work from A. Rashki and R. Dégano is acknowledged. C. albicans strains SC5314 and GU5 were kind gifts from Dr.␣Joachim Morschhauser, Germany. We specially thank Dr.␣Joachim Ernst, Germany, for sharing the hypoxia related microarray data with us. We thank Ranbaxy Laboratories (New Delhi, India) for providing fluconazole.

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Authors and Affiliations

  1. Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India

    Dibyendu Banerjee, Sudhanshu Shukla & Rajendra Prasad

  2. SpecialCentre for Molecular Medicine, JNU, New Delhi, India

    Dibyendu Banerjee & Gauranga Mukhopadhyay

  3. Instituto de Microbiología Bioquímica/Departamento de Microbiología y Genética, CSIC/Universidad de Salamanca, Salamanca, Spain

    Nuria Martin & Angel Dominguez

  4. Center For Computational Biology and Bioinformatics, School of Information Technology, JNU, New Delhi, India

    Soumyadeep Nandi

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  1. Dibyendu Banerjee
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  2. Nuria Martin
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Correspondence to Rajendra Prasad.

Electronic supplementary material

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11046_2007_9025_MOESM1_ESM.doc

List of genes that were up-regulated or down-regulated by progesterone treatment in the microarray experiments (DOC 375 kb)

11046_2007_9025_MOESM2_ESM.doc

Table showing the presence of various transcription factor binding sites in the −1000 bp (with respect to ATG) sequence of progesterone responsive genes found in the microarray experiments (DOC 241 kb)

(DOC 242 kb)

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Banerjee, D., Martin, N., Nandi, S. et al. A genome-wide steroid response study of the major human fungal pathogen Candida albicans . Mycopathologia 164, 1–17 (2007). https://doi.org/10.1007/s11046-007-9025-8

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