Ribosomal Protein L40e Fused With a Ubiquitin Moiety Is Essential for the Vegetative Growth, Morphological Homeostasis, Cell Cycle Progression, and Pathogenicity of Cryptococcus neoformans
Ubiquitin is a highly conserved protein required for various fundamental cellular processes in eukaryotes. Herein, we first report the contribution of the ubiquitin fusion protein Ubi1 (a ubiquitin monomer fused with the ribosome protein L40e, Rpl40e) in the growth and pathogenicity of Cryptococcus...
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2020.570269/full |
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| author | Jingyu Zhao Jingyu Zhao Yali Yang Yali Yang Yibin Fan Jiu Yi Chao Zhang Zhongkai Gu Weihua Pan Julin Gu Wanqing Liao Wei Fang |
| author_facet | Jingyu Zhao Jingyu Zhao Yali Yang Yali Yang Yibin Fan Jiu Yi Chao Zhang Zhongkai Gu Weihua Pan Julin Gu Wanqing Liao Wei Fang |
| author_sort | Jingyu Zhao |
| collection | DOAJ |
| description | Ubiquitin is a highly conserved protein required for various fundamental cellular processes in eukaryotes. Herein, we first report the contribution of the ubiquitin fusion protein Ubi1 (a ubiquitin monomer fused with the ribosome protein L40e, Rpl40e) in the growth and pathogenicity of Cryptococcus neoformans. UBI1 deletion resulted in severe growth restriction of C. neoformans, whose growth rate was positively correlated with UBI1 expression level. The growth defect of the ubi1Δ strain could be closely associated with its morphological abnormalities, such as its reduced ribosome particles. In addition, the ubi1Δ mutant also displayed increased cell ploidy, cell cycle arrest, and decreased intracellular survival inside macrophages. All these phenotypes were reversed by the reconstitution of the full-length UBI1 gene or RPL40a domain. Mouse survival and fungal burden assays further revealed a severely attenuated pathogenicity for the ubi1Δ mutant, which is probably associated with its reduced stress tolerance and the induction of T-helper 1-type immune response. Taken together, Ubi1 is required for maintaining the vegetative growth, morphological homeostasis, cell cycle progression, and pathogenicity in vivo of C. neoformans. The pleiotropic roles of Ubi1 are dependent on the presence of Rpl40e and associated with its regulation of cryptococcal ribosome biogenesis. |
| format | Article |
| id | doaj-art-462d6cbe72924bf7ae9884cc0c7ca1b6 |
| institution | Kabale University |
| issn | 1664-302X |
| language | English |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-462d6cbe72924bf7ae9884cc0c7ca1b62025-01-09T09:01:36ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-11-011110.3389/fmicb.2020.570269570269Ribosomal Protein L40e Fused With a Ubiquitin Moiety Is Essential for the Vegetative Growth, Morphological Homeostasis, Cell Cycle Progression, and Pathogenicity of Cryptococcus neoformansJingyu Zhao0Jingyu Zhao1Yali Yang2Yali Yang3Yibin Fan4Jiu Yi5Chao Zhang6Zhongkai Gu7Weihua Pan8Julin Gu9Wanqing Liao10Wei Fang11Shanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai, ChinaDepartment of Dermatology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, ChinaShanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai, ChinaDepartment of Dermatology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Dermatology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaShanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai, ChinaShanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai, ChinaThe Institute of Biomedical Sciences, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai, ChinaDepartment of Dermatology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, ChinaShanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai, ChinaShanghai Key Laboratory of Molecular Medical Mycology, Department of Dermatology, Changzheng Hospital, Second Military Medical University, Shanghai, ChinaUbiquitin is a highly conserved protein required for various fundamental cellular processes in eukaryotes. Herein, we first report the contribution of the ubiquitin fusion protein Ubi1 (a ubiquitin monomer fused with the ribosome protein L40e, Rpl40e) in the growth and pathogenicity of Cryptococcus neoformans. UBI1 deletion resulted in severe growth restriction of C. neoformans, whose growth rate was positively correlated with UBI1 expression level. The growth defect of the ubi1Δ strain could be closely associated with its morphological abnormalities, such as its reduced ribosome particles. In addition, the ubi1Δ mutant also displayed increased cell ploidy, cell cycle arrest, and decreased intracellular survival inside macrophages. All these phenotypes were reversed by the reconstitution of the full-length UBI1 gene or RPL40a domain. Mouse survival and fungal burden assays further revealed a severely attenuated pathogenicity for the ubi1Δ mutant, which is probably associated with its reduced stress tolerance and the induction of T-helper 1-type immune response. Taken together, Ubi1 is required for maintaining the vegetative growth, morphological homeostasis, cell cycle progression, and pathogenicity in vivo of C. neoformans. The pleiotropic roles of Ubi1 are dependent on the presence of Rpl40e and associated with its regulation of cryptococcal ribosome biogenesis.https://www.frontiersin.org/articles/10.3389/fmicb.2020.570269/fullCryptococcus neoformansubiquitingrowth restrictioncellular morphologyvirulenceimmune evasion |
| spellingShingle | Jingyu Zhao Jingyu Zhao Yali Yang Yali Yang Yibin Fan Jiu Yi Chao Zhang Zhongkai Gu Weihua Pan Julin Gu Wanqing Liao Wei Fang Ribosomal Protein L40e Fused With a Ubiquitin Moiety Is Essential for the Vegetative Growth, Morphological Homeostasis, Cell Cycle Progression, and Pathogenicity of Cryptococcus neoformans Frontiers in Microbiology Cryptococcus neoformans ubiquitin growth restriction cellular morphology virulence immune evasion |
| title | Ribosomal Protein L40e Fused With a Ubiquitin Moiety Is Essential for the Vegetative Growth, Morphological Homeostasis, Cell Cycle Progression, and Pathogenicity of Cryptococcus neoformans |
| title_full | Ribosomal Protein L40e Fused With a Ubiquitin Moiety Is Essential for the Vegetative Growth, Morphological Homeostasis, Cell Cycle Progression, and Pathogenicity of Cryptococcus neoformans |
| title_fullStr | Ribosomal Protein L40e Fused With a Ubiquitin Moiety Is Essential for the Vegetative Growth, Morphological Homeostasis, Cell Cycle Progression, and Pathogenicity of Cryptococcus neoformans |
| title_full_unstemmed | Ribosomal Protein L40e Fused With a Ubiquitin Moiety Is Essential for the Vegetative Growth, Morphological Homeostasis, Cell Cycle Progression, and Pathogenicity of Cryptococcus neoformans |
| title_short | Ribosomal Protein L40e Fused With a Ubiquitin Moiety Is Essential for the Vegetative Growth, Morphological Homeostasis, Cell Cycle Progression, and Pathogenicity of Cryptococcus neoformans |
| title_sort | ribosomal protein l40e fused with a ubiquitin moiety is essential for the vegetative growth morphological homeostasis cell cycle progression and pathogenicity of cryptococcus neoformans |
| topic | Cryptococcus neoformans ubiquitin growth restriction cellular morphology virulence immune evasion |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2020.570269/full |
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