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Published on: October 12, 2022
Regulation of filamentation in the human fungal pathogen Candida tropicalis
Qiuyu Zhang1,2, Li Tao1, Guobo Guan1
1State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Abstract:
The yeast-filament transition is essential for the virulence of a variety of fungi that are pathogenic to humans. N-acetylglucosamine (GlcNAc) is a potent inducer of filamentation in Candida albicans and thermally dimorphic fungi such as Histoplasma capsulatum and Blastomyces dermatitidis. However, GlcNAc suppresses rather than promotes filamentation in Candida tropicalis, a fungal species that is closely related to C. albicans. Despite the intensive study in C. albicans, the regulatory mechanism of filamentation is poorly understood. In this study, we demonstrate that the cAMP signaling pathway plays a central role in the regulation of filamentation in C. tropicalis. By screening an overexpression library of 156 transcription factors, we have identified approximately 40 regulators of filamentous growth. Although most of the regulators (e.g., Tec1, Gat2, Nrg1, Sfl1, Sfl2 and Ash1) demonstrate a conserved role in the regulation of filamentation, similar to their homologues in C. albicans or Saccharomyces cerevisiae, a number of transcription factors (e.g., Wor1, Bcr1, Stp4, Efh1, Csr1 and Zcf17) play a specific role in C. tropicalis. Our findings indicate that multiple interconnected signaling pathways are involved in the regulation of filamentation in C. tropicalis. These mechanisms have conserved and divergent features among different Candida species.
Insights
N-acetylglucosamine (GlcNAc) induces filamentation in most fungi, but suppresses it in Candida tropicalis. This study reveals the cAMP signaling pathway and specific transcription factors regulate this crucial fungal transition in C. tropicalis.
Area of Science:
- Mycology
- Molecular Biology
- Medical Mycology
Background:
- The yeast-to-filament transition is critical for the virulence of human fungal pathogens.
- N-acetylglucosamine (GlcNAc) induces filamentation in many fungi, but paradoxically suppresses it in Candida tropicalis.
Purpose of the Study:
- To elucidate the regulatory mechanisms of filamentation in Candida tropicalis.
- To identify key signaling pathways and transcription factors involved in GlcNAc-mediated filamentation control.
Main Methods:
- Screening of an overexpression library containing 156 transcription factors.
- Analysis of conserved and species-specific regulators of filamentous growth.
Main Results:
- The cAMP signaling pathway is central to filamentation regulation in C. tropicalis.
- Approximately 40 regulators of filamentous growth were identified.
- Identified both conserved regulators (e.g., Tec1, Nrg1) and novel, C. tropicalis-specific factors (e.g., Wor1, Bcr1).
Conclusions:
- Multiple interconnected signaling pathways regulate filamentation in C. tropicalis.
- These regulatory mechanisms exhibit both conserved and divergent features across Candida species.
- Understanding these pathways is crucial for targeting fungal virulence.
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