Related Experiment Video
Updated: Jul 9, 2025
Live-cell Video Microscopy of Fungal Pathogen Phagocytosis
Published on: January 9, 2013
Respiration supports intraphagosomal filamentation and escape of Candida albicans from macrophages
Nicola T Case1, Johannes Westman2, Michael T Hallett3
1Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Importance:
Candida albicans is a leading human fungal pathogen that often causes life-threatening infections in immunocompromised individuals. The ability of C. albicans to transition between yeast and filamentous forms is key to its virulence, and this occurs in response to many host-relevant cues, including engulfment by host macrophages. While previous efforts identified C. albicans genes required for filamentation in other conditions, the genes important for this morphological transition upon internalization by macrophages remained largely enigmatic. Here, we employed a functional genomic approach to identify genes that enable C. albicans filamentation within macrophages and uncovered a role for the mitochondrial ribosome, respiration, and the SNF1 AMP-activated kinase complex. Additionally, we showed that glucose uptake and glycolysis by macrophages support C. albicans filamentation. This work provides insights into the metabolic dueling that occurs during the interaction of C. albicans with macrophages and identifies vulnerabilities in C. albicans that could serve as promising therapeutic targets.
Insights
Candida albicans filamentation within macrophages depends on its mitochondria and respiration. Macrophage glucose metabolism also fuels this fungal transition, revealing potential therapeutic targets.
Area of Science:
- Mycology
- Infectious Diseases
- Cell Biology
Background:
- Candida albicans is a major human fungal pathogen causing severe infections in immunocompromised individuals.
- Morphological transition from yeast to filament is crucial for C. albicans virulence, often triggered by host macrophages.
- Genes regulating this transition within macrophages are largely unknown.
Purpose of the Study:
- To identify genes enabling Candida albicans filamentation inside macrophages using functional genomics.
- To understand the metabolic interplay between C. albicans and macrophages during infection.
Main Methods:
- Functional genomic screening of Candida albicans mutants within macrophages.
- Analysis of gene expression and metabolic pathways.
Main Results:
- Identified essential roles for the mitochondrial ribosome, respiration, and SNF1 AMP-activated kinase complex in macrophage-induced filamentation.
- Demonstrated that macrophage glucose uptake and glycolysis support C. albicans filamentation.
- Revealed metabolic competition between the fungus and host cell.
Conclusions:
- Candida albicans filamentation within macrophages is metabolically regulated, involving mitochondrial function and host glucose.
- Targeting these fungal pathways presents potential therapeutic strategies against C. albicans infections.
More Related Videos
08:48Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
09:24Use 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
