AUTHOR=Amorim-Vaz Sara , Coste Alix T. , Tran Van Du T. , Pagni Marco , Sanglard Dominique 

TITLE=Function Analysis of MBF1, a Factor Involved in the Response to Amino Acid Starvation and Virulence in Candida albicans

JOURNAL=Frontiers in Fungal Biology

VOLUME=2

YEAR=2021

URL=https://www.frontiersin.org/journals/fungal-biology/articles/10.3389/ffunb.2021.658899

DOI=10.3389/ffunb.2021.658899

ISSN=2673-6128

ABSTRACT=<p><italic>Candida albicans</italic> 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 <italic>C. albicans</italic> is able to cause disease and how it copes with the host defenses. Our previous studies have revealed the importance of the <italic>C. albicans</italic> gene <italic>MBF1</italic> in virulence and ability to colonize internal organs of mammalian and insect hosts. <italic>MBF1</italic> encodes a putative transcriptional regulator, and as such it likely has an impact in the regulation of <italic>C. albicans</italic> gene expression during host infection. Here, recent advances in RNA-seq technologies were used to obtain a detailed analysis of the impact of <italic>MBF1</italic> on <italic>C. albicans</italic> gene expression both <italic>in vitro</italic> and during infection. <italic>MBF1</italic> 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 <italic>MBF1</italic> and <italic>GCN4</italic>, 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 <italic>MBF1</italic> in virulence, we also established that <italic>GCN4</italic> was necessary for virulence in the mouse model of systemic infection as well as in the <italic>Galleria mellonella</italic> infection model.</p>