Cargando…
A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformans
Infection of Cryptococcus neoformans is one of the leading causes of morbidity and mortality, particularly among immunocompromised patients. However, currently available drugs for the treatment of C. neoformans infection are minimal. Here, we report SP1, a peptide derived from glyceraldehyde-3-phosp...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8754130/ https://www.ncbi.nlm.nih.gov/pubmed/35019693 http://dx.doi.org/10.1128/spectrum.00826-21 |
_version_ | 1784632209708154880 |
---|---|
author | Zhang, Yang Zhou, Liyan Liu, Yan Zhao, Xi Lian, Xianqiang Zhang, Jie Zhao, De Wang, Yujuan Zhong, Jin Wang, Junfeng Wang, Hongli Wang, Linqi Fu, Yu V. |
author_facet | Zhang, Yang Zhou, Liyan Liu, Yan Zhao, Xi Lian, Xianqiang Zhang, Jie Zhao, De Wang, Yujuan Zhong, Jin Wang, Junfeng Wang, Hongli Wang, Linqi Fu, Yu V. |
author_sort | Zhang, Yang |
collection | PubMed |
description | Infection of Cryptococcus neoformans is one of the leading causes of morbidity and mortality, particularly among immunocompromised patients. However, currently available drugs for the treatment of C. neoformans infection are minimal. Here, we report SP1, a peptide derived from glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of Saccharomyces cerevisiae, efficiently kills C. neoformans and Cryptococcus gattii. SP1 causes damages to the capsule. Unlike many antimicrobial peptides, SP1 does not form pores on the cell membrane of C. neoformans. It interacts with membrane ergosterol and enters vacuole possibly through membrane trafficking. C. neoformans treated with SP1 show the apoptotic phenotypes such as imbalance of calcium ion homeostasis, reactive oxygen increment, phosphatidylserine exposure, and nuclear fragmentation. Our data imply that SP1 has the potential to be developed into a treatment option for cryptococcosis. IMPORTANCE Cryptococcus neoformans and Cryptococcus gattii can cause cryptococcosis, which has a high mortality rate. To treat the disease, amphotericin B and fluconazole are often used in clinic. However, amphotericin B has rather high renal toxicity, and tolerance to these drugs are quicky developed. The peptide SP1 derived from baker’s yeast GAPDH shows antifungal function to kill Cryptococcus neoformans and Cryptococcus gattii efficiently with a high specificity, even for the drug-resistant strains. Our data demonstrate that SP1 induces the apoptosis-like death of Cryptococcus neoformans at low concentrations. The finding of this peptide may shed light on a new direction to treat cryptococcosis. |
format | Online Article Text |
id | pubmed-8754130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-87541302022-01-24 A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformans Zhang, Yang Zhou, Liyan Liu, Yan Zhao, Xi Lian, Xianqiang Zhang, Jie Zhao, De Wang, Yujuan Zhong, Jin Wang, Junfeng Wang, Hongli Wang, Linqi Fu, Yu V. Microbiol Spectr Research Article Infection of Cryptococcus neoformans is one of the leading causes of morbidity and mortality, particularly among immunocompromised patients. However, currently available drugs for the treatment of C. neoformans infection are minimal. Here, we report SP1, a peptide derived from glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of Saccharomyces cerevisiae, efficiently kills C. neoformans and Cryptococcus gattii. SP1 causes damages to the capsule. Unlike many antimicrobial peptides, SP1 does not form pores on the cell membrane of C. neoformans. It interacts with membrane ergosterol and enters vacuole possibly through membrane trafficking. C. neoformans treated with SP1 show the apoptotic phenotypes such as imbalance of calcium ion homeostasis, reactive oxygen increment, phosphatidylserine exposure, and nuclear fragmentation. Our data imply that SP1 has the potential to be developed into a treatment option for cryptococcosis. IMPORTANCE Cryptococcus neoformans and Cryptococcus gattii can cause cryptococcosis, which has a high mortality rate. To treat the disease, amphotericin B and fluconazole are often used in clinic. However, amphotericin B has rather high renal toxicity, and tolerance to these drugs are quicky developed. The peptide SP1 derived from baker’s yeast GAPDH shows antifungal function to kill Cryptococcus neoformans and Cryptococcus gattii efficiently with a high specificity, even for the drug-resistant strains. Our data demonstrate that SP1 induces the apoptosis-like death of Cryptococcus neoformans at low concentrations. The finding of this peptide may shed light on a new direction to treat cryptococcosis. American Society for Microbiology 2022-01-12 /pmc/articles/PMC8754130/ /pubmed/35019693 http://dx.doi.org/10.1128/spectrum.00826-21 Text en Copyright © 2022 Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Zhang, Yang Zhou, Liyan Liu, Yan Zhao, Xi Lian, Xianqiang Zhang, Jie Zhao, De Wang, Yujuan Zhong, Jin Wang, Junfeng Wang, Hongli Wang, Linqi Fu, Yu V. A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformans |
title | A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformans |
title_full | A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformans |
title_fullStr | A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformans |
title_full_unstemmed | A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformans |
title_short | A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformans |
title_sort | peptide from budding yeast gapdh serves as a promising antifungal against cryptococcus neoformans |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8754130/ https://www.ncbi.nlm.nih.gov/pubmed/35019693 http://dx.doi.org/10.1128/spectrum.00826-21 |
work_keys_str_mv | AT zhangyang apeptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT zhouliyan apeptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT liuyan apeptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT zhaoxi apeptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT lianxianqiang apeptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT zhangjie apeptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT zhaode apeptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT wangyujuan apeptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT zhongjin apeptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT wangjunfeng apeptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT wanghongli apeptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT wanglinqi apeptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT fuyuv apeptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT zhangyang peptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT zhouliyan peptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT liuyan peptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT zhaoxi peptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT lianxianqiang peptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT zhangjie peptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT zhaode peptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT wangyujuan peptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT zhongjin peptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT wangjunfeng peptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT wanghongli peptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT wanglinqi peptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans AT fuyuv peptidefrombuddingyeastgapdhservesasapromisingantifungalagainstcryptococcusneoformans |