Abstract
As a human fungal pathogen, Candida albicans can cause a wide variety of disease conditions ranging from superficial to systemic infections. Many of these infections are caused by an inherent ability of the pathogen to form biofilms on medical devices resulting in high mortality. Biofilms formed by C. albicans are a complex consortium of yeast and hyphal cells embedded in an extracellular matrix and are regulated by a network of transcription factors. Here, we report the role of a novel Zn(II)2-Cys6 binuclear cluster transcription factor, ZCF32, in the regulation of biofilm formation. Global transcriptome analysis reveals that biofilm development is the most altered pathway in the zcf32 null mutant. To delineate the functional correlation between ZCF32 and biofilm development, we determined the set of genes directly regulated by Zcf32. Our data suggests that Zcf32 regulates biofilm formation by repressing the expression of adhesins, chitinases and a significant number of other GPI-anchored proteins. We establish that there is the lesser recruitment of Zcf32 on the promoters of biofilm genes in biofilm condition compared to the planktonic mode of growth. Taking together, we propose that the transcription factor ZCF32 negatively regulates biofilm development in C. albicans.
Highlights
To elucidate the role of ZCF32, it was deleted from C. albicans wild-type SC5314 strain using the SAT1 flipper cassette strategy[28] and the desired homozygous mutants were identified by Southern blot analysis (Supplementary Fig. S1C)
As we show that ZCF32 negatively regulates biofilm development, the Chromatin immunoprecipitation (ChIP)- qPCR analysis was carried out from YPK104 cells grown in the biofilm mode of growth
We show that the fungal specific Zn(II)2Cys[6] transcription factor, ZCF32 represses the development of biofilm in C. albicans
Summary
Adhesion is the first and crucial step during biofilm growth and the role of various cell wall proteins and transcription factors in the process has been demonstrated[15,16,17,18,19]. We report the role of a novel transcription factor, ZCF32, in the repression of biofilm development. The genome-wide expression analysis, the selective evolution of ligands by exponential enrichment (SELEX) and ChIP- qPCR data revealed that ZCF32 negatively regulates biofilm formation. We show that this newly identified transcription factor negatively regulates the adhesion and filamentation processes by repressing the expression of adhesins and various cell wall proteins. More recruitment of Zcf[32] on the promoters of biofilm genes is observed in the planktonic condition as compared to the biofilm condition confirming the negative impact of ZCF32 on the biofilm pathway
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