Per O. Ljungdahl
Professor in Cell Biology, Stockholm University University, Dept Molecular Biosciences, Wenner-Gren Institute
Metabolic and spatio-temporal determinants of fungal virulence
Humans are hosts to a wide range of commensal microorganisms. The microflora consists largely of prokaryotes, but eukaryotic fungi are also important with Candida spp. being dominant. Several Candida spp. are capable of causing life-threatening infections in immunocompromised individuals. Since the incidence of Candida infections is low in healthy populations, primary immune cells are key to restricting virulent growth. Candida albicans, the major cause of human mycoses, can switch morphologies from yeast-like to filamentous forms, a virulence property linked to macrophage escape and invasive growth through epithelial barriers. We recently identified proline catabolism as essential for inducing and supplying the energy for filamentous growth. Based on this new knowledge, we are pursuing three experimental aims. First, we are dissecting the metabolic control of proline-dependent virulence with a particular focus on mitochondria-localized processes critical for fungal cell survival. Second, using intra vital 2-photon microscopy we have visualized the spatio-temporal aspects of C. albicans infections in the kidney of a living mammalian host (mouse) and, currently in collaboration, are working to precisely define host-pathogen interactions by STED microscopy and spatio-transcriptomic analysis. Third, we are investigating proline catabolism in Candida auris, a new and significant global threat to human health.
- Fitz Gerald S Silao, senior researcher
- Ioanna Myronidi, PhD student
- Biborka Bereczky Veress, senior researcher