An expanded cell wall damage signaling network is comprised of the transcription factors Rlm1 and Sko1 in Candida albicans

Autoři: Marienela Y. Heredia aff001;  Mélanie A. C. Ikeh aff002;  Deepika Gunasekaran aff002;  Karen A. Conrad aff001;  Sviatlana Filimonava aff001;  Dawn H. Marotta aff001;  Clarissa J. Nobile aff002;  Jason M. Rauceo aff001
Působiště autorů: Department of Sciences, John Jay College of the City University of New York, New York, New York, United States of America aff001;  Department of Molecular and Cell Biology, School of Natural Sciences, University of California Merced, Merced, California, United States of America aff002;  Quantitative and Systems Biology Graduate Program, University of California Merced, Merced, California, United States of America aff003
Vyšlo v časopise: An expanded cell wall damage signaling network is comprised of the transcription factors Rlm1 and Sko1 in Candida albicans. PLoS Genet 16(7): e32767. doi:10.1371/journal.pgen.1008908
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008908


The human fungal pathogen Candida albicans is constantly exposed to environmental challenges impacting the cell wall. Signaling pathways coordinate stress adaptation and are essential for commensalism and virulence. The transcription factors Sko1, Cas5, and Rlm1 control the response to cell wall stress caused by the antifungal drug caspofungin. Here, we expand the Sko1 and Rlm1 transcriptional circuit and demonstrate that Rlm1 activates Sko1 cell wall stress signaling. Caspofungin-induced transcription of SKO1 and several Sko1-dependent cell wall integrity genes are attenuated in an rlm1Δ/Δ mutant strain when compared to the treated wild-type strain but not in a cas5Δ/Δ mutant strain. Genome-wide chromatin immunoprecipitation (ChIP-seq) results revealed numerous Sko1 and Rlm1 directly bound target genes in the presence of caspofungin that were undetected in previous gene expression studies. Notable targets include genes involved in cell wall integrity, osmolarity, and cellular aggregation, as well as several uncharacterized genes. Interestingly, we found that Rlm1 does not bind to the upstream intergenic region of SKO1 in the presence of caspofungin, indicating that Rlm1 indirectly controls caspofungin-induced SKO1 transcription. In addition, we discovered that caspofungin-induced SKO1 transcription occurs through self-activation. Based on our ChIP-seq data, we also discovered an Rlm1 consensus motif unique to C. albicans. For Sko1, we found a consensus motif similar to the known Sko1 motif for Saccharomyces cerevisiae. Growth assays showed that SKO1 overexpression suppressed caspofungin hypersensitivity in an rlm1Δ/Δ mutant strain. In addition, overexpression of the glycerol phosphatase, RHR2, suppressed caspofungin hypersensitivity specifically in a sko1Δ/Δ mutant strain. Our findings link the Sko1 and Rlm1 signaling pathways, identify new biological roles for Sko1 and Rlm1, and highlight the complex dynamics underlying cell wall signaling.

Klíčová slova:

Candida albicans – Cell walls – Gene regulation – Microarrays – Mutant strains – Osmotic shock – Stress signaling cascade – Transcriptional control


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