Abstract
Metabolic adaptation is linked to the ability of the opportunistic pathogen Candida albicans to colonize and cause infection in diverse host tissues. One way that C. albicans controls its metabolism is through the glucose repression pathway, where expression of alternative carbon source utilization genes is repressed in the presence of its preferred carbon source, glucose. Here we carry out genetic and gene expression studies that identify transcription factors Mig1 and Mig2 as mediators of glucose repression in C. albicans. The well-studied Mig1/2 orthologs ScMig1/2 mediate glucose repression in the yeast Saccharomyces cerevisiae; our data argue that C. albicans Mig1/2 function similarly as repressors of alternative carbon source utilization genes. However, Mig1/2 functions have several distinctive features in C. albicans. First, Mig1 and Mig2 have more co-equal roles in gene regulation than their S. cerevisiae orthologs. Second, Mig1 is regulated at the level of protein accumulation, more akin to ScMig2 than ScMig1. Third, Mig1 and Mig2 are together required for a unique aspect of C. albicans biology, the expression of several pathogenicity traits. Such Mig1/2-dependent traits include the abilities to form hyphae and biofilm, tolerance of cell wall inhibitors, and ability to damage macrophage-like cells and human endothelial cells. Finally, Mig1 is required for a puzzling feature of C. albicans biology that is not shared with S. cerevisiae: the essentiality of the Snf1 protein kinase, a central eukaryotic carbon metabolism regulator. Our results integrate Mig1 and Mig2 into the C. albicans glucose repression pathway and illuminate connections among carbon control, pathogenicity, and Snf1 essentiality.
Highlights
Carbon metabolism is central to the growth and survival of all organisms
To investigate C. albicans gene expression response to carbon, we compared cells growing on the non-fermentable carbon source glycerol to those growing on glucose
RNA-sequencing (RNA-seq) was performed on wild-type C. albicans in YPG (Yeast Peptone Glycerol) and YPD (Yeast Peptone Dextrose) media grown to log phase at 37 ̊C
Summary
Carbon metabolism is central to the growth and survival of all organisms. It provides both energy and biosynthetic building blocks. It is tightly controlled in most organisms to enable optimal use of diverse carbon sources. Our focus is the fungus Candida albicans. It exists primarily as a commensal resident of the GI and GU tracts of humans and other warm-blooded animals. The ability of C. albicans to cause infection of diverse tissues and body sites depends upon its ability to regulate the utilization of diverse carbon sources [4]
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