Projects per year
Abstract
The yeast Candida albicans colonizes several sites in the human body and responds to metabolic signals in commensal and pathogenic states. The yeast-to-hyphae transition correlates with virulence, but how metabolic status is integrated with this transition is incompletely understood. We used the putative mitochondrial fission inhibitor mdivi-1 to probe the crosstalk between hyphal signaling and metabolism. Mdivi-1 repressed C. albicans hyphal morphogenesis, but the mechanism was independent of its presumed target, the mitochondrial fission GTPase Dnm1. Instead, mdivi-1 triggered extensive metabolic reprogramming, consistent with metabolic stress, and reduced endogenous nitric oxide (NO) levels. Limiting endogenous NO stabilized the transcriptional repressor Nrg1 and inhibited the yeast-to-hyphae transition. We establish a role for endogenous NO signaling in C. albicans hyphal morphogenesis and suggest that NO regulates a metabolic checkpoint for hyphal growth. Furthermore, identifying NO signaling as an mdivi-1 target could inform its therapeutic applications in human diseases. Hyphal morphogenesis contributes to virulence of the human fungal pathogen Candida albicans. Koch et al. show that mdivi-1, a putative inhibitor of mitochondrial division, represses hyphal growth of Candida and implicate regulation of endogenous nitric oxide levels in the mechanism of action of mdivi-1 and the regulation of hyphal morphogenesis.
Original language | English |
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Pages (from-to) | 2244-2258 |
Number of pages | 15 |
Journal | Cell Reports |
Volume | 25 |
Issue number | 8 |
DOIs | |
Publication status | Published - 20 Nov 2018 |
Keywords
- Candida albicans
- fungal pathogenesis
- hyphae
- mdivi-1
- metabolism
- mitochondria
- morphogenesis
- mycology
- nitric oxide
Projects
- 2 Finished
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The mechanism and function of 3'UTR switching in eukaryotic cells
Australian Research Council (ARC), Monash University
1/03/17 → 31/12/19
Project: Research
Press / Media
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Monash researchers reveal how a deadly fungal infection shape-shifts into an invasive monster
21/11/18
1 Media contribution
Press/Media: Research
Equipment
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Bioinformatics Platform
David Powell (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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Monash Micro Imaging
Stephen Firth (Manager), Alex Fulcher (Operator), Oleks Chernyavskiy (Operator), Margaret Rzeszutek (Other), David Potter (Manager), Volker Hilsenstein (Operator), Juan Nunez-Iglesias (Other), Stephen Cody (Manager), Irena Carmichael (Operator), Betty Kouskousis (Other), Sarah Creed (Manager) & Giulia Ballerin (Operator)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility
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Monash Proteomics & Metabolomics Facility
Ralf Schittenhelm (Manager)
Faculty of Medicine Nursing and Health Sciences Research PlatformsFacility/equipment: Facility