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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...

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Autores principales: 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.
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
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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.
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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
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