Roles of Candida albicans Mig1 and Mig2 in glucose repression, pathogenicity traits, and SNF1 essentiality.
Animals
Biofilms
Candida albicans
/ drug effects
Cell Line
Drug Resistance, Fungal
Endothelial Cells
/ microbiology
Fungal Proteins
/ genetics
Gene Expression Regulation, Fungal
Glucose
/ metabolism
Humans
Macrophages
/ microbiology
Mice
Protein Serine-Threonine Kinases
/ metabolism
Transcription Factors
/ genetics
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
15
08
2019
accepted:
20
12
2019
revised:
31
01
2020
pubmed:
22
1
2020
medline:
14
4
2020
entrez:
22
1
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31961865
doi: 10.1371/journal.pgen.1008582
pii: PGENETICS-D-19-01346
pmc: PMC6994163
doi:
Substances chimiques
Fungal Proteins
0
Transcription Factors
0
SNF1-related protein kinases
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008582Subventions
Organisme : NIAID NIH HHS
ID : R01 AI124566
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE026600
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI144878
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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