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P4-ATPase subunit Cdc50 plays a role in yeast budding and cell wall integrity in Candida glabrata

BACKGROUND: As highly-conserved types of lipid flippases among fungi, P4-ATPases play a significant role in various cellular processes. Cdc50 acts as the regulatory subunit of flippases, forming heterodimers with Drs2 to translocate aminophospholipids. Cdc50 homologs have been reported to be implica...

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Autores principales: Chen, Ke-Zhi, Wang, Lu-Ling, Liu, Jin-Yan, Zhao, Jun-Tao, Huang, Si-Jia, Xiang, Ming-Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10100066/
https://www.ncbi.nlm.nih.gov/pubmed/37046215
http://dx.doi.org/10.1186/s12866-023-02810-3
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author Chen, Ke-Zhi
Wang, Lu-Ling
Liu, Jin-Yan
Zhao, Jun-Tao
Huang, Si-Jia
Xiang, Ming-Jie
author_facet Chen, Ke-Zhi
Wang, Lu-Ling
Liu, Jin-Yan
Zhao, Jun-Tao
Huang, Si-Jia
Xiang, Ming-Jie
author_sort Chen, Ke-Zhi
collection PubMed
description BACKGROUND: As highly-conserved types of lipid flippases among fungi, P4-ATPases play a significant role in various cellular processes. Cdc50 acts as the regulatory subunit of flippases, forming heterodimers with Drs2 to translocate aminophospholipids. Cdc50 homologs have been reported to be implicated in protein trafficking, drug susceptibility, and virulence in Saccharomyces cerevisiae, Candida albicans and Cryptococcus neoformans. It is likely that Cdc50 has an extensive influence on fungal cellular processes. The present study aimed to determine the function of Cdc50 in Candida glabrata by constructing a Δcdc50 null mutant and its complemented strain. RESULTS: In Candida glabrata, the loss of Cdc50 led to difficulty in yeast budding, probably caused by actin depolarization. The Δcdc50 mutant also showed hypersensitivity to azoles, caspofungin, and cell wall stressors. Further experiments indicated hyperactivation of the cell wall integrity pathway in the Δcdc50 mutant, which elevated the major cell wall contents. An increase in exposure of β-(1,3)-glucan and chitin on the cell surface was also observed through flow cytometry. Interestingly, we observed a decrease in the phagocytosis rate when the Δcdc50 mutant was co-incubated with THP-1 macrophages. The Δcdc50 mutant also exhibited weakened virulence in nematode survival tests. CONCLUSION: The results suggested that the lipid flippase subunit Cdc50 is implicated in yeast budding and cell wall integrity in C. glabrata, and thus have a broad influence on drug susceptibility and virulence. This work highlights the importance of lipid flippase, and offers potential targets for new drug research.
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spelling pubmed-101000662023-04-14 P4-ATPase subunit Cdc50 plays a role in yeast budding and cell wall integrity in Candida glabrata Chen, Ke-Zhi Wang, Lu-Ling Liu, Jin-Yan Zhao, Jun-Tao Huang, Si-Jia Xiang, Ming-Jie BMC Microbiol Research BACKGROUND: As highly-conserved types of lipid flippases among fungi, P4-ATPases play a significant role in various cellular processes. Cdc50 acts as the regulatory subunit of flippases, forming heterodimers with Drs2 to translocate aminophospholipids. Cdc50 homologs have been reported to be implicated in protein trafficking, drug susceptibility, and virulence in Saccharomyces cerevisiae, Candida albicans and Cryptococcus neoformans. It is likely that Cdc50 has an extensive influence on fungal cellular processes. The present study aimed to determine the function of Cdc50 in Candida glabrata by constructing a Δcdc50 null mutant and its complemented strain. RESULTS: In Candida glabrata, the loss of Cdc50 led to difficulty in yeast budding, probably caused by actin depolarization. The Δcdc50 mutant also showed hypersensitivity to azoles, caspofungin, and cell wall stressors. Further experiments indicated hyperactivation of the cell wall integrity pathway in the Δcdc50 mutant, which elevated the major cell wall contents. An increase in exposure of β-(1,3)-glucan and chitin on the cell surface was also observed through flow cytometry. Interestingly, we observed a decrease in the phagocytosis rate when the Δcdc50 mutant was co-incubated with THP-1 macrophages. The Δcdc50 mutant also exhibited weakened virulence in nematode survival tests. CONCLUSION: The results suggested that the lipid flippase subunit Cdc50 is implicated in yeast budding and cell wall integrity in C. glabrata, and thus have a broad influence on drug susceptibility and virulence. This work highlights the importance of lipid flippase, and offers potential targets for new drug research. BioMed Central 2023-04-13 /pmc/articles/PMC10100066/ /pubmed/37046215 http://dx.doi.org/10.1186/s12866-023-02810-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Chen, Ke-Zhi
Wang, Lu-Ling
Liu, Jin-Yan
Zhao, Jun-Tao
Huang, Si-Jia
Xiang, Ming-Jie
P4-ATPase subunit Cdc50 plays a role in yeast budding and cell wall integrity in Candida glabrata
title P4-ATPase subunit Cdc50 plays a role in yeast budding and cell wall integrity in Candida glabrata
title_full P4-ATPase subunit Cdc50 plays a role in yeast budding and cell wall integrity in Candida glabrata
title_fullStr P4-ATPase subunit Cdc50 plays a role in yeast budding and cell wall integrity in Candida glabrata
title_full_unstemmed P4-ATPase subunit Cdc50 plays a role in yeast budding and cell wall integrity in Candida glabrata
title_short P4-ATPase subunit Cdc50 plays a role in yeast budding and cell wall integrity in Candida glabrata
title_sort p4-atpase subunit cdc50 plays a role in yeast budding and cell wall integrity in candida glabrata
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10100066/
https://www.ncbi.nlm.nih.gov/pubmed/37046215
http://dx.doi.org/10.1186/s12866-023-02810-3
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