ArticlePLoS genetics2020
An expanded cell wall damage signaling network is comprised of the transcription factors Rlm1 and Sko1 in Candida albicans.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 28 citations in OpenAlex.
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- Resilience in Resistance: The Role of Cell Wall Integrity in Multidrug-Resistant Candida.Journal of fungi (Basel, Switzerland) · 2025Review
- Candida albicans' inorganic phosphate transport and evolutionary adaptation to phosphate scarcity.PLoS genetics · 2024Article
- Associations of Rap1 with Cell Wall Integrity, Biofilm Formation, and Virulence in Candida albicans.Microbiology spectrum · 2022Article
- The Role of Sfp1 inJournal of fungi (Basel, Switzerland) · 2022Article
- Monoclonal Antibodies Targeting Surface-Exposed Epitopes of Candida albicans Cell Wall Proteins ConferAntimicrobial agents and chemotherapy · 2022Article
- The prophylactic effects of monoclonal antibodies targeting the cell wall Pmt4 protein epitopes ofFrontiers in microbiology · 2022Article
- The SPFH Protein Superfamily in Fungi: Impact on Mitochondrial Function and Implications in Virulence.Microorganisms · 2021Review
- CWI pathway participated in vegetative growth and pathogenicity through a downstream effector AflRlm1 iniScience · 2021Article
- The SAGA and NuA4 component Tra1 regulates Candida albicans drug resistance and pathogenesis.Genetics · 2021Article
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- Fungal Cell Wall Proteins and Signaling Pathways Form a Cytoprotective Network to Combat Stresses.Journal of fungi (Basel, Switzerland) · 2021Review
- Environmentally contingent control of Candida albicans cell wall integrity by transcriptional regulator Cup9.Genetics · 2021Article
- The Roles of Chromatin Accessibility in Regulating theJournal of fungi (Basel, Switzerland) · 2021Review
- Transcriptional regulation of the caspofungin-induced cell wall damage response in Candida albicans.Current genetics · 2020Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
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.
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