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Roles of Candida albicans Mig1 and Mig2 in glucose repression, pathogenicity traits, and SNF1 essentiality


Autoři: Katherine Lagree aff001;  Carol A. Woolford aff001;  Manning Y. Huang aff001;  Gemma May aff001;  C. Joel McManus aff001;  Norma V. Solis aff002;  Scott G. Filler aff002;  Aaron P. Mitchell aff001
Působiště autorů: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America aff001;  Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America aff002;  Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America aff003;  Department of Microbiology, University of Georgia, Athens, Georgia, United States of America aff004
Vyšlo v časopise: Roles of Candida albicans Mig1 and Mig2 in glucose repression, pathogenicity traits, and SNF1 essentiality. PLoS Genet 16(1): e32767. doi:10.1371/journal.pgen.1008582
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008582

Souhrn

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.

Klíčová slova:

Biofilms – Candida albicans – Gene expression – Glucose – Glucose metabolism – Macrophages – Mutant strains – Saccharomyces cerevisiae


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