A genome-wide steroid response study of the major human fungal pathogen Candida albicans.
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; AG(4) or C(4)T) 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.
Banerjee
Dibyendu
D
Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Martin
Nuria
N
Nandi
Soumyadeep
S
Shukla
Sudhanshu
S
Dominguez
Angel
A
Mukhopadhyay
Gauranga
G
Prasad
Rajendra
R
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D015152:Blotting, Northern; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D002177:Candidiasis / Q000382:microbiology; D025141:Drug Resistance, Fungal / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D016681:Genome, Fungal; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011374:Progesterone / Q000494:pharmacology*
D018528:ATP-Binding Cassette Transporters; D005656:Fungal Proteins; D011374:Progesterone