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Understanding the Role of ZCF32, a Zinc Cluster Transcription Factor, in Candida albicans Biology

Electronic Theses of Indian Institute of Science

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Title Understanding the Role of ZCF32, a Zinc Cluster Transcription Factor, in Candida albicans Biology
 
Creator Kakade, Pallavi
 
Subject ZCF32 - Zinc Cluster
ZCF32 - Candida Albicans Biology
Candida Albicans Biology - Virulence Factors
Electrophoretic Mobility Shift Assay
Zinc Finger TFs
C. albicans
Zn(II)2Cys6 Zinc Binuclear Cluster Transcription Factors
Zn(II)2 Cys6 Transcription Factor
Zinc Cluster Proteins
Microbiology and Cell Biology
 
Description 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, I 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, the set of genes directly regulated by Zcf32 were determined. The data suggest that Zcf32 regulates biofilm formation by repressing the expression of adhesins, chitinases and a significant number of other GPI-anchored proteins. The data presented here 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. Thus, the transcription factor ZCF32 negatively regulates biofilm development in C. albicans.
Candida albicans, carries an expanded family of Zn(II)2Cys6 transcription factors. A CTG clade-specific protein Zcf32 and its closely related protein Upc2, a well-conserved protein across the various fungal species, belong to this family of proteins. Unlike Upc2, Zcf32 is poorly studied in C. albicans. Here, I examined roles played by these two related transcription factors in biofilm development and virulence of C. albicans. The data show that the null mutants of each of ZCF32 or UPC2 form better biofilms than the wild-type suggesting that both of them negatively regulate the biofilm development. While acting as negative regulators of biofilm formation, these two transcription factors target a different set of biofilm genes. A mouse model of candidiasis reveals that zcf32/zcf32 was hypervirulent while upc2/upc2 shows compromised virulence compared to the wild-type. Notably, the absence of Zcf32 enhances detrimental inflammation brought about by TNFα, IFNβ, and IFNγ. upc2/upc2 failed to generate a similar feedback, instead demonstrated an elevated anti-inflammatory (IL4 and IL10) host response. Taking together, the data exhibit how a recently evolved transcription factor Zcf32 retained functional resemblance with a more ubiquitous member Upc2 but also functionally diverged from the latter in the regulation of virulence of the pathogen.
 
Contributor Sadhale, Parag
 
Date 2018-05-25T15:51:53Z
2018-05-25T15:51:53Z
2018-05-25
2017
 
Type Thesis
 
Identifier http://etd.iisc.ernet.in/2005/3626
http://etd.iisc.ernet.in/abstracts/4496/G28468-Abs.pdf
 
Language en_US
 
Relation G28468