| Title: | Glucosamine stimulates pheromone-independent dimorphic transition in Cryptococcus neoformans by promoting Crz1 nuclear translocation |
| Author(s): | Xu X; Lin J; Zhao Y; Kirkman E; So YS; Bahn YS; Lin X; |
| Address: | "Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. Department of Biology, Texas A&M University, College Station, Texas, United States of America. Department of Microbiology, University of Georgia, Athens, Georgia, United States of America. Department of Biotechnology, Yonsei University, Seoul, Korea" |
| DOI: | 10.1371/journal.pgen.1006982 |
| ISSN/ISBN: | 1553-7404 (Electronic) 1553-7390 (Print) 1553-7390 (Linking) |
| Abstract: | "Morphotype switch is a cellular response to external and internal cues. The Cryptococcus neoformans species complex can undergo morphological transitions between the yeast and the hypha form, and such morphological changes profoundly affect cryptococcal interaction with various hosts. Filamentation in Cryptococcus was historically considered a mating response towards pheromone. Recent studies indicate the existence of pheromone-independent signaling pathways but their identity or the effectors remain unknown. Here, we demonstrated that glucosamine stimulated the C. neoformans species complex to undergo self-filamentation. Glucosamine-stimulated filamentation was independent of the key components of the pheromone pathway, which is distinct from pheromone-elicited filamentation. Glucosamine stimulated self-filamentation in H99, a highly virulent serotype A clinical isolate and a widely used reference strain. Through a genetic screen of the deletion sets made in the H99 background, we found that Crz1, a transcription factor downstream of calcineurin, was essential for glucosamine-stimulated filamentation despite its dispensability for pheromone-mediated filamentation. Glucosamine promoted Crz1 translocation from the cytoplasm to the nucleus. Interestingly, multiple components of the high osmolality glycerol response (HOG) pathway, consisting of the phosphorelay system and some of the Hog1 MAPK module, acted as repressors of glucosamine-elicited filamentation through their calcineurin-opposing effect on Crz1's nuclear translocation. Surprisingly, glucosamine-stimulated filamentation did not require Hog1 itself and was distinct from the conventional general stress response. The results demonstrate that Cryptococcus can resort to multiple genetic pathways for morphological transition in response to different stimuli. Given that the filamentous form attenuates cryptococcal virulence and is immune-stimulatory in mammalian models, the findings suggest that morphogenesis is a fertile ground for future investigation into novel means to compromise cryptococcal pathogenesis" |
| Keywords: | Calcineurin/metabolism Cell Nucleus/genetics/metabolism Cryptococcus neoformans/*genetics/growth & development Cytoplasm/genetics/metabolism Fungal Proteins/*genetics/metabolism Glucosamine/*metabolism Hyphae/genetics/growth & development Mitogen-Activate; |
| Notes: | "MedlineXu, Xinping Lin, Jianfeng Zhao, Youbao Kirkman, Elyssa So, Yee-Seul Bahn, Yong-Sun Lin, Xiaorong eng R01 AI097599/AI/NIAID NIH HHS/ 2017/09/13 PLoS Genet. 2017 Sep 12; 13(9):e1006982. doi: 10.1371/journal.pgen.1006982. eCollection 2017 Sep" |
