A Novel Role for the Transcription Factor Cwt1p as a Negative Regulator of Nitrosative Stress in Candida albicans

  1. Get@NRC: A Novel Role for the Transcription Factor Cwt1p as a Negative Regulator of Nitrosative Stress in Candida albicans (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1371/journal.pone.0043956
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Journal titlePLoS ONE
Article numbere43956
Subjecttranscription factor; transcription factor Cwt1p; unclassified drug; article; Candida albicans; controlled study; fungal genome; fungus mutant; gene activation; gene expression; gene expression profiling; gene location; gene regulatory network; gene repression; genetic analysis; host cell; nitrosative stress; nonhuman; phagocyte; regulon; transcription regulation; Candida albicans; Fungal Proteins; Gene Expression Profiling; Gene Expression Regulation, Fungal; Genomics; Oxygenases; Promoter Regions, Genetic; Reactive Nitrogen Species; Stress, Physiological; Transcription Factors; Transcription, Genetic; Candida albicans; Fungi; Mammalia
AbstractThe ability of Candida albicans to survive in the presence of nitrosative stress during the initial contact with the host immune system is crucial for its ability to colonize mammalian hosts. Thus, this fungus must activate robust mechanisms to neutralize and repair nitrosative-induced damage. Until now, very little was known regarding the regulatory circuits associated with reactive nitrogen species detoxification in fungi. To gain insight into the transcriptional regulatory networks controlling nitrosative stress response (NRS) in C. albicans a compilation of transcriptional regulator-defective mutants were screened. This led to the identification of Cwt1p as a negative regulator of NSR. By combining genome-wide location and expression analyses, we have characterized the Cwt1p regulon and demonstrated that Cwt1p is directly required for proper repression of the flavohemoglobin Yhb1p, a key NO-detoxification enzyme. Furthermore, Cwt1p operates both by activating and repressing genes of specific functions solicited upon NSR. Additionally, we used Gene Set Enrichment Analysis to reinvestigate the C. albicans NSR-transcriptome and demonstrate a significant similarity with the transcriptional profiles of C. albicans interacting with phagocytic host-cells. In summary, we have characterized a novel negative regulator of NSR and bring new insights into the transcriptional regulatory network governing fungal NSR. © 2012 Sellam et al.
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AffiliationNational Research Council Canada (NRC-CNRC); NRC Biotechnology Research Institute (BRI-IRB)
Peer reviewedYes
NPARC number21269180
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Record identifier34be012a-2267-48bd-9143-3d9a9efd673f
Record created2013-12-12
Record modified2016-05-09
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