A unique cell wall synthetic response evoked by glucosamine determines pathogenicity-associated fungal cellular differentiation.
The yeast-to-hypha transition is tightly associated with pathogenicity in many human pathogenic fungi, such as the model fungal pathogen Cryptococcus neoformans, which is responsible for approximately 180,000 deaths annually. In this pathogen, the yeast-to-hypha transition can be initiated by distin...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-10-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1009817 |
| _version_ | 1818402856925921280 |
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| author | Pengjie Hu Hao Ding Lan Shen Guang-Jun He Huimin Liu Xiuyun Tian Changyu Tao Xiangzheng Bai Jingnan Liang Cheng Jin Xinping Xu Ence Yang Linqi Wang |
| author_facet | Pengjie Hu Hao Ding Lan Shen Guang-Jun He Huimin Liu Xiuyun Tian Changyu Tao Xiangzheng Bai Jingnan Liang Cheng Jin Xinping Xu Ence Yang Linqi Wang |
| author_sort | Pengjie Hu |
| collection | DOAJ |
| description | The yeast-to-hypha transition is tightly associated with pathogenicity in many human pathogenic fungi, such as the model fungal pathogen Cryptococcus neoformans, which is responsible for approximately 180,000 deaths annually. In this pathogen, the yeast-to-hypha transition can be initiated by distinct stimuli: mating stimulation or glucosamine (GlcN), the monomer of cell wall chitosan. However, it remains poorly understood how the signal specificity for Cryptococcus morphological transition by disparate stimuli is ensured. Here, by integrating temporal expression signature analysis and phenome-based clustering evaluation, we demonstrate that GlcN specifically triggers a unique cellular response, which acts as a critical determinant underlying the activation of GlcN-induced filamentation (GIF). This cellular response is defined by an unusually hyperactive cell wall synthesis that is highly ATP-consuming. A novel cell surface protein Gis1 was identified as the indicator molecule for the GlcN-induced cell wall response. The Mpk1-directed cell wall pathway critically bridges global cell wall gene induction and intracellular ATP supply, ensuring the Gis1-dependent cell wall response and the stimulus specificity of GIF. We further reveal that the ability of Mpk1 to coordinate the cell wall response and GIF activation is conserved in different Cryptococcus pathogens. Phosphoproteomics-based profiling together with genetic and phenotypic analysis revealed that the Mpk1 kinase mediates the regulatory specificity of GIF through a coordinated downstream regulatory network centered on Skn7 and Crz1. Overall, our findings discover an unprecedented and conserved cell wall biosynthesis-dependent fungal differentiation commitment mechanism, which enables the signal specificity of pathogenicity-related dimorphism induced by GlcN in Cryptococcus pathogens. |
| first_indexed | 2024-12-14T08:15:01Z |
| format | Article |
| id | doaj.art-960598d8e0284623ad635d6dda2be985 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-14T08:15:01Z |
| publishDate | 2021-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-960598d8e0284623ad635d6dda2be9852022-12-21T23:09:56ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-10-011710e100981710.1371/journal.pgen.1009817A unique cell wall synthetic response evoked by glucosamine determines pathogenicity-associated fungal cellular differentiation.Pengjie HuHao DingLan ShenGuang-Jun HeHuimin LiuXiuyun TianChangyu TaoXiangzheng BaiJingnan LiangCheng JinXinping XuEnce YangLinqi WangThe yeast-to-hypha transition is tightly associated with pathogenicity in many human pathogenic fungi, such as the model fungal pathogen Cryptococcus neoformans, which is responsible for approximately 180,000 deaths annually. In this pathogen, the yeast-to-hypha transition can be initiated by distinct stimuli: mating stimulation or glucosamine (GlcN), the monomer of cell wall chitosan. However, it remains poorly understood how the signal specificity for Cryptococcus morphological transition by disparate stimuli is ensured. Here, by integrating temporal expression signature analysis and phenome-based clustering evaluation, we demonstrate that GlcN specifically triggers a unique cellular response, which acts as a critical determinant underlying the activation of GlcN-induced filamentation (GIF). This cellular response is defined by an unusually hyperactive cell wall synthesis that is highly ATP-consuming. A novel cell surface protein Gis1 was identified as the indicator molecule for the GlcN-induced cell wall response. The Mpk1-directed cell wall pathway critically bridges global cell wall gene induction and intracellular ATP supply, ensuring the Gis1-dependent cell wall response and the stimulus specificity of GIF. We further reveal that the ability of Mpk1 to coordinate the cell wall response and GIF activation is conserved in different Cryptococcus pathogens. Phosphoproteomics-based profiling together with genetic and phenotypic analysis revealed that the Mpk1 kinase mediates the regulatory specificity of GIF through a coordinated downstream regulatory network centered on Skn7 and Crz1. Overall, our findings discover an unprecedented and conserved cell wall biosynthesis-dependent fungal differentiation commitment mechanism, which enables the signal specificity of pathogenicity-related dimorphism induced by GlcN in Cryptococcus pathogens.https://doi.org/10.1371/journal.pgen.1009817 |
| spellingShingle | Pengjie Hu Hao Ding Lan Shen Guang-Jun He Huimin Liu Xiuyun Tian Changyu Tao Xiangzheng Bai Jingnan Liang Cheng Jin Xinping Xu Ence Yang Linqi Wang A unique cell wall synthetic response evoked by glucosamine determines pathogenicity-associated fungal cellular differentiation. PLoS Genetics |
| title | A unique cell wall synthetic response evoked by glucosamine determines pathogenicity-associated fungal cellular differentiation. |
| title_full | A unique cell wall synthetic response evoked by glucosamine determines pathogenicity-associated fungal cellular differentiation. |
| title_fullStr | A unique cell wall synthetic response evoked by glucosamine determines pathogenicity-associated fungal cellular differentiation. |
| title_full_unstemmed | A unique cell wall synthetic response evoked by glucosamine determines pathogenicity-associated fungal cellular differentiation. |
| title_short | A unique cell wall synthetic response evoked by glucosamine determines pathogenicity-associated fungal cellular differentiation. |
| title_sort | unique cell wall synthetic response evoked by glucosamine determines pathogenicity associated fungal cellular differentiation |
| url | https://doi.org/10.1371/journal.pgen.1009817 |
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