A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformans
ABSTRACT 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 glyceraldehyd...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-02-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00826-21 |
| _version_ | 1819279598278410240 |
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| author | Yang Zhang Liyan Zhou Yan Liu Xi Zhao Xianqiang Lian Jie Zhang De Zhao Yujuan Wang Jin Zhong Junfeng Wang Hongli Wang Linqi Wang Yu V. Fu |
| author_facet | Yang Zhang Liyan Zhou Yan Liu Xi Zhao Xianqiang Lian Jie Zhang De Zhao Yujuan Wang Jin Zhong Junfeng Wang Hongli Wang Linqi Wang Yu V. Fu |
| author_sort | Yang Zhang |
| collection | DOAJ |
| description | ABSTRACT 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. |
| first_indexed | 2024-12-24T00:30:27Z |
| format | Article |
| id | doaj.art-7b351cdb38354fa4982a607f1391dc64 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-12-24T00:30:27Z |
| publishDate | 2022-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-7b351cdb38354fa4982a607f1391dc642022-12-21T17:24:16ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-02-0110110.1128/spectrum.00826-21A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformansYang Zhang0Liyan Zhou1Yan Liu2Xi Zhao3Xianqiang Lian4Jie Zhang5De Zhao6Yujuan Wang7Jin Zhong8Junfeng Wang9Hongli Wang10Linqi Wang11Yu V. Fu12School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaHigh Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaHigh Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, ChinaDepartment of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, ChinaABSTRACT 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.https://journals.asm.org/doi/10.1128/spectrum.00826-21antifungal peptideGAPDHCryptococcus neoformansapoptosis |
| spellingShingle | Yang Zhang Liyan Zhou Yan Liu Xi Zhao Xianqiang Lian Jie Zhang De Zhao Yujuan Wang Jin Zhong Junfeng Wang Hongli Wang Linqi Wang Yu V. Fu A Peptide from Budding Yeast GAPDH Serves as a Promising Antifungal against Cryptococcus neoformans Microbiology Spectrum antifungal peptide GAPDH Cryptococcus neoformans apoptosis |
| 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 | antifungal peptide GAPDH Cryptococcus neoformans apoptosis |
| url | https://journals.asm.org/doi/10.1128/spectrum.00826-21 |
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