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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Function Analysis of MBF1, a Factor Involved in the Response to Amino Acid Starvation and Virulence in Candida
Sara Amorim-Vaz1, Alix T Coste1, Van Du T Tran2
1Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland.
Abstract:
Candida albicans is a commensal of human mucosae, but also one of the most common fungal pathogens of humans. Systemic infections caused by this fungus, mostly affecting immunocompromised patients, are associated to fatality rates as high as 50% despite the available treatments. In order to improve this situation, it is necessary to fully understand how C. albicans is able to cause disease and how it copes with the host defenses. Our previous studies have revealed the importance of the C. albicans gene MBF1 in virulence and ability to colonize internal organs of mammalian and insect hosts. MBF1 encodes a putative transcriptional regulator, and as such it likely has an impact in the regulation of C. albicans gene expression during host infection. Here, recent advances in RNA-seq technologies were used to obtain a detailed analysis of the impact of MBF1 on C. albicans gene expression both in vitro and during infection. MBF1 was involved in the regulation of several genes with a role in glycolysis and response to stress, particularly to nutritional stress. We also investigated whether an interaction existed between MBF1 and GCN4, a master regulator of response to starvation, and found that both genes were needed for resistance to amino acid starvation, suggesting some level of interaction between the two. Reinforcing this idea, we showed that the proteins encoded by both genes could interact. Consistent with the role of MBF1 in virulence, we also established that GCN4 was necessary for virulence in the mouse model of systemic infection as well as in the Galleria mellonella infection model.
Insights
The Candida albicans MBF1 gene regulates genes involved in glycolysis and stress response. MBF1 and GCN4 interact to enable resistance to starvation and are crucial for fungal virulence in hosts.
Area of Science:
- Mycology
- Molecular Biology
- Pathogenesis
Background:
- Candida albicans is a common human fungal pathogen causing life-threatening systemic infections, especially in immunocompromised individuals.
- Understanding C. albicans virulence mechanisms and host defense interactions is critical for improving treatment outcomes.
- The C. albicans gene MBF1 has been previously identified as important for virulence and organ colonization.
Purpose of the Study:
- To analyze the impact of MBF1 on C. albicans gene expression during in vitro and in vivo conditions using RNA-seq.
- To investigate the potential interaction between MBF1 and GCN4, a known regulator of starvation response.
- To determine the role of MBF1 and GCN4 in host defense and fungal virulence.
Main Methods:
- RNA sequencing (RNA-seq) to profile gene expression changes.
- In vitro assays to assess gene function and protein interactions.
- In vivo infection models (mouse and Galleria mellonella) to evaluate virulence.
Main Results:
- MBF1 regulates genes involved in glycolysis and stress responses, particularly nutritional stress.
- MBF1 and GCN4 are both essential for resistance to amino acid starvation.
- Physical interaction between MBF1 and GCN4 proteins was demonstrated.
- GCN4 is required for C. albicans virulence in systemic infection models.
Conclusions:
- MBF1 plays a significant role in regulating gene expression related to nutrient metabolism and stress adaptation in C. albicans.
- MBF1 and GCN4 exhibit functional and physical interactions, highlighting a coordinated response to starvation.
- Both MBF1 and GCN4 are critical for C. albicans pathogenesis, emphasizing their importance in fungal virulence.
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