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.

Frontiers in Fungal Biology
|September 25, 2023
PubMed

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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