Nat Microbiol. 2026 Jan;11(1):169-179. doi: 10.1038/s41564-025-02205-2
Decreased cytoplasmic crowding via inhibition of ribosome biogenesis can trigger Candida albicans filamentous growth
Antonio Serrano1,2, Charles Puerner#1,3, Louis Chevalier#1, Emily Plumb1, Johannes Elferich4,5, Stephen Diggs4, Ludwig Roman Sinn6, Nikolaus Grigorieff4,5, Markus Ralser6,7,8, Morgan Delarue9, Martine Bassilana1, Robert Alan Arkowitz10
Affiliations
1Université Côte d’Azur, CNRS, INSERM, Institute of Biology Valrose (iBV), Nice, France.
2Centro de Biotecnología y Genómica de Plantas, Universidad Politécnica de Madrid (UPM)-Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA/CSIC), Pozuelo de Alarcón, Spain.
3Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
4RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.
5Howard Hughes Medical Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.
6Department of Biochemistry, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
7Berlin Institute of Health (BIH) at Charité-Universitätsmedizin Berlin, Berlin, Germany.
8Max Planck Institute for Molecular Genetics, Berlin, Germany.
9LAAS-CNRS, University of Toulouse, CNRS, Toulouse, France.
10Université Côte d’Azur, CNRS, INSERM, Institute of Biology Valrose (iBV), Nice, France.
#Contributed equally.
Abstract
The human fungal pathogen Candida albicans undergoes a morphological transition from a budding yeast to a filamentous form, which is associated with pathogenesis. Various cues mediate this transition including intracellular reorganization. The cytoplasm is densely packed with proteins including large macromolecular complexes, such as ribosomes, and hence, molecular crowding can impact a range of cellular processes. However, the relationship between cytoplasmic molecular crowding and morphological growth states is unclear. Using a fluorescent microrheological probe and single particle tracking, we observed a striking decrease in molecular crowding during filamentous growth in C. albicans. On the basis of simulations, proteomics and structural data from in situ cryogenic electron microscopy, we show that the reduction in crowding is due to a decrease in ribosome concentration that results in part from an inhibition of ribosome biogenesis, combined with an increase in cytoplasmic volume, leading to a dilution of ribosomes. Filamentation was enhanced in a mutant defective in ribosome biogenesis, while translation was not affected, suggesting that inhibition of ribosome biogenesis is a trigger for C. albicans morphogenesis. Overall, we show that filamentous growth is associated with reduced cytoplasmic crowding via changes in ribosome concentration, suggesting that combination therapies in which ribosome biogenesis is also targeted may be advantageous.