ArticleProceedings of the National Academy of Sciences of the United States of America2014
Quorum sensing controls hyphal initiation in Candida albicans through Ubr1-mediated protein degradation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 103 citations in OpenAlex.
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- Transdermal administration of farnesol-ethosomes enhances the treatment of cutaneous candidiasis induced byMicrobiology spectrum · 2024Article
- Physiological adventures inMicrobiology and molecular biology reviews : MMBR · 2024Review
- Studying mixed-species biofilms of Candida albicans and Staphylococcus aureus using evolutionary game theory.PloS one · 2024Article
- Transcriptional regulation of the synthesis and secretion of farnesol in the fungus Candida albicans: examination of the Homann transcription regulator knockout collection.G3 (Bethesda, Md.) · 2023Article
- Apoptotic Factors, CaNma111 and CaYbh3, Function in Candida albicans Filamentation by Regulating the Hyphal Suppressors, Nrg1 and Tup1.Journal of microbiology (Seoul, Korea) · 2023Review
- Fungal resilience and host-pathogen interactions: Future perspectives and opportunities.Parasite immunology · 2023Review
- Antifungal and Antibiofilm Efficacy of Paeonol Treatment Against Biofilms ComprisingFrontiers in cellular and infection microbiology · 2022Article
- The transcription factor Cas5 suppresses hyphal morphogenesis during yeast-form growth in Candida albicans.Journal of microbiology (Seoul, Korea) · 2021Article
- Environmentally contingent control of Candida albicans cell wall integrity by transcriptional regulator Cup9.Genetics · 2021Article
- From Jekyll to Hyde: The Yeast-Hyphal Transition ofPathogens (Basel, Switzerland) · 2021Review
- Ubr1-mediated ubiquitylation orchestrates asexual development, polar growth, and virulence-related cellular events in Beauveria bassiana.Applied microbiology and biotechnology · 2021Article
- Functional connections between cell cycle and proteostasis in the regulation of Candida albicans morphogenesis.Cell reports · 2021Review
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4 authors at 1 institution in 1 country.
Funding
Abstract
Candida albicans is the most common cause of invasive fungal infections in humans. Its ability to undergo the morphological transition from yeast to hyphal growth forms is critical for its pathogenesis. Hyphal initiation requires the activation of the cAMP-PKA pathway, which down-regulates the expression of NRG1, the major repressor of hyphal development. Hyphal initiation also requires inoculation of a small amount of C. albicans cells from overnight culture to fresh medium. This inoculation releases the inhibition from farnesol, a quorum-sensing molecule of C. albicans, that accumulated in the spent medium. Here, we show that farnesol inhibits hyphal initiation mainly through blocking the protein degradation of Nrg1. Through screening a kinase mutant library, we identified Sok1 as the kinase required for Nrg1 degradation during inoculation. SOK1 expression is transiently activated on inoculation during hyphal initiation, and overexpression of SOK1 overcomes the farnesol-mediated inhibition of hyphal initiation. Screening a collection of transcription factor mutants, the homeodomain-containing transcription repressor Cup9 is found to be responsible for the repression of SOK1 expression in response to farnesol inhibition. Interestingly, farnesol inhibits Cup9 degradation mediated by the N-end rule E3 ubiquitin ligase, Ubr1. Therefore, hyphal initiation requires both the cAMP-PKA pathway-dependent transcriptional down-regulation of NRG1 and Sok1-mediated degradation of Nrg1 protein. The latter is triggered by the release from farnesol inhibition of Cup9 degradation and consequently, derepression of SOK1 transcription. Neither pathway alone is sufficient for hyphal initiation.
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