Two negative regulators of biofilm development exhibit functional divergence in conferring virulence potential to Candida albicans

Kakade, Pallavi and Mahadik, Kasturi and Balaji, Kithiganahalli Narayanaswamy and Sanyal, Kaustuv and Nagaraja, Valakunja (2018) Two negative regulators of biofilm development exhibit functional divergence in conferring virulence potential to Candida albicans. In: FEMS YEAST RESEARCH, 19 (2).

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Abstract

Candida albicans, a human pathogen, carries an expanded family of Zn(II)2Cys6 transcription factors. A CTG Glade-specific protein Zcf32 and its closely related protein Upc2, a well-conserved transcription factor across the various fungal species, belong to this family of proteins. Unlike Upc2, Zcf32 is poorly studied in C. albicans. Here, we examined roles played by these two related transcription factors in biofilm development and virulence of C. albicans. Our 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 bio film 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 TNF alpha, IFN beta and IFN gamma. upc2/upc2 failed to generate a similar feedback, instead demonstrated an elevated anti-inflammatory (IL4 and IL10) host response. Taking together, we show 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 biofilm development and virulence of the pathogen.

Item Type:	Journal Article
Publication:	FEMS YEAST RESEARCH
Publisher:	OXFORD UNIV PRESS
Additional Information:	The copyright for this article belongs to Oxford University Press
Keywords:	Candida; transcription factors; biofilm; virulence; pathogenesis
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	29 Apr 2019 07:45
Last Modified:	29 Apr 2019 07:45
URI:	http://eprints.iisc.ac.in/id/eprint/62555

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