Two negative regulators of biofilm development exhibit functional divergence in conferring virulence potential toCandida albicans
| Autor: | Pallavi Kakade, Kaustuv Sanyal, Valakunja Nagaraja, Kasturi Mahadik, Kithiganahalli Narayanaswamy Balaji |
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| Rok vydání: | 2018 |
| Předmět: |
Virulence
Biology Applied Microbiology and Biotechnology Microbiology 03 medical and health sciences Gene Expression Regulation Fungal Candida albicans Animals Gene Pathogen Transcription factor 030304 developmental biology Inflammation Microbiology & Cell Biology Mice Inbred BALB C 0303 health sciences 030306 microbiology Candidiasis Biofilm General Medicine biology.organism_classification Corpus albicans Disease Models Animal Biofilms Gene Deletion Functional divergence Transcription Factors |
| Zdroj: | FEMS Yeast Research. 19 |
| ISSN: | 1567-1364 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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