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Use of In Vivo Imaging to Screen for Morphogenesis Phenotypes in Candida albicans Mutant Strains During Active Infection in a Mammalian Host
Published on: October 12, 2022
Mds3 regulates morphogenesis in Candida albicans through the TOR pathway
Lucia F Zacchi1, Jonatan Gomez-Raja, Dana A Davis
1Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Mds3 regulates the yeast-to-hypha transition in Candida albicans by interacting with the TOR pathway. This discovery sheds light on fungal pathogen morphogenesis and survival strategies.
Area of Science:
- Microbiology
- Molecular Biology
- Mycology
Background:
- Candida albicans is a significant human fungal pathogen.
- Morphogenesis, specifically the yeast-to-hypha transition, is crucial for C. albicans survival and virulence.
- Mds3 is a newly identified regulator of pH-dependent morphogenesis.
Purpose of the Study:
- To investigate the role of Mds3 in Candida albicans morphogenesis.
- To determine the relationship between Mds3 and the Target Of Rapamycin (TOR) pathway.
- To elucidate the molecular mechanisms underlying Mds3 function.
Main Methods:
- Microarray analysis to assess gene expression profiles in mds3 mutant cells.
- Treatment with rapamycin, a TOR inhibitor, to observe rescue effects.
- Genetic analysis using TOR1-1 and rbp1 deletion mutants.
- Co-immunoprecipitation to assess protein interactions.
Main Results:
- Mds3 deletion resulted in a hyperactive TOR pathway signature, with altered ribosomal protein and nitrogen utilization gene expression.
- Rapamycin rescued the transcriptional and morphological defects of mds3 mutants, an effect dependent on TOR1 and RBP1.
- Rapamycin also rescued defects in sit4 mutants, but not rim101 or ras1 mutants, indicating Mds3 and Sit4 function within the TOR pathway.
- Mds3 and Sit4 were found to co-immunoprecipitate.
Conclusions:
- Mds3 is a novel component of the TOR pathway in C. albicans.
- Mds3 plays a critical role in regulating morphogenesis through its interaction with the TOR pathway.
- Mds3 and Sit4 likely function together within the TOR pathway to control fungal development and virulence.
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