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Allicin shows antifungal efficacy against Cryptococcus neoformans by blocking the fungal cell membrane

Allicin, which is generated by the catalytic reaction between alliin and alliinase extracted from garlic, has been shown to have a wide range of antimicrobial activities, but its anti-Cryptococcus efficacy and mechanism are not quite clear. Here, we have determined that the Conversion rate of allici...

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Autores principales: Li, Zhun, Li, Zhengtu, Yang, Jun, Lu, Chun, Li, Yongming, Luo, Yinzhu, Cong, Feng, Shi, Rongmei, Wang, Zhen, Chen, Huaying, Li, Xinxia, Yang, Jinglu, Ye, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709445/
https://www.ncbi.nlm.nih.gov/pubmed/36466672
http://dx.doi.org/10.3389/fmicb.2022.1012516
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author Li, Zhun
Li, Zhengtu
Yang, Jun
Lu, Chun
Li, Yongming
Luo, Yinzhu
Cong, Feng
Shi, Rongmei
Wang, Zhen
Chen, Huaying
Li, Xinxia
Yang, Jinglu
Ye, Feng
author_facet Li, Zhun
Li, Zhengtu
Yang, Jun
Lu, Chun
Li, Yongming
Luo, Yinzhu
Cong, Feng
Shi, Rongmei
Wang, Zhen
Chen, Huaying
Li, Xinxia
Yang, Jinglu
Ye, Feng
author_sort Li, Zhun
collection PubMed
description Allicin, which is generated by the catalytic reaction between alliin and alliinase extracted from garlic, has been shown to have a wide range of antimicrobial activities, but its anti-Cryptococcus efficacy and mechanism are not quite clear. Here, we have determined that the Conversion rate of allicin in the reaction product reached 97.5%. The minimal inhibitory concentration (MIC) of allicin against Cryptococcus neoformans (C. neoformans) H99 was 2 μg/ml, which is comparable to fluconazole (FLU, 1 μg/ml). Furthermore, allicin exhibited effective antifungal activity against 46 clinical isolates of C. neoformans, and the MICs ranged from 1 to 8 μg/ml, even for AmB-insensitive strains. Interestingly, allicin also exerted additive or synergistic effects when combined with amphotericin B (AmB) and FLU. Time-killing curves and long-term live cell imaging of H99 showed that 4 MIC of allicin had fungicide activity. Additionally, allicin (4 and 8 mg/kg) exerted a dose-dependent therapeutic effect on H99-infected mice by significantly reducing the wet pulmonary coefficient and Cryptococcus load and reducing lung damage. Even the efficacy of 8 mg/kg was comparable to FLU (20 mg/kg). Transcriptomics revealed that allicin may act on the cell membrane of H99. Subsequently, transmission electron microscopy (TEM) observations showed that allicin clearly breached the cell membrane and organelles of H99. Confocal laser scanning microscopy (CLSM) results further confirmed that allicin disrupted the permeability of the cell membranes of H99 in a dose-dependent manner. Allicin exhibits strong anti-C. neoformans activity in vitro and in vivo, mainly by destroying the permeability and related functions of Cryptococcus cell membranes.
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spelling pubmed-97094452022-12-01 Allicin shows antifungal efficacy against Cryptococcus neoformans by blocking the fungal cell membrane Li, Zhun Li, Zhengtu Yang, Jun Lu, Chun Li, Yongming Luo, Yinzhu Cong, Feng Shi, Rongmei Wang, Zhen Chen, Huaying Li, Xinxia Yang, Jinglu Ye, Feng Front Microbiol Microbiology Allicin, which is generated by the catalytic reaction between alliin and alliinase extracted from garlic, has been shown to have a wide range of antimicrobial activities, but its anti-Cryptococcus efficacy and mechanism are not quite clear. Here, we have determined that the Conversion rate of allicin in the reaction product reached 97.5%. The minimal inhibitory concentration (MIC) of allicin against Cryptococcus neoformans (C. neoformans) H99 was 2 μg/ml, which is comparable to fluconazole (FLU, 1 μg/ml). Furthermore, allicin exhibited effective antifungal activity against 46 clinical isolates of C. neoformans, and the MICs ranged from 1 to 8 μg/ml, even for AmB-insensitive strains. Interestingly, allicin also exerted additive or synergistic effects when combined with amphotericin B (AmB) and FLU. Time-killing curves and long-term live cell imaging of H99 showed that 4 MIC of allicin had fungicide activity. Additionally, allicin (4 and 8 mg/kg) exerted a dose-dependent therapeutic effect on H99-infected mice by significantly reducing the wet pulmonary coefficient and Cryptococcus load and reducing lung damage. Even the efficacy of 8 mg/kg was comparable to FLU (20 mg/kg). Transcriptomics revealed that allicin may act on the cell membrane of H99. Subsequently, transmission electron microscopy (TEM) observations showed that allicin clearly breached the cell membrane and organelles of H99. Confocal laser scanning microscopy (CLSM) results further confirmed that allicin disrupted the permeability of the cell membranes of H99 in a dose-dependent manner. Allicin exhibits strong anti-C. neoformans activity in vitro and in vivo, mainly by destroying the permeability and related functions of Cryptococcus cell membranes. Frontiers Media S.A. 2022-11-16 /pmc/articles/PMC9709445/ /pubmed/36466672 http://dx.doi.org/10.3389/fmicb.2022.1012516 Text en Copyright © 2022 Li, Li, Yang, Lu, Li, luo, Cong, Shi, Wang, Chen, Li, Yang and Ye. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Li, Zhun
Li, Zhengtu
Yang, Jun
Lu, Chun
Li, Yongming
Luo, Yinzhu
Cong, Feng
Shi, Rongmei
Wang, Zhen
Chen, Huaying
Li, Xinxia
Yang, Jinglu
Ye, Feng
Allicin shows antifungal efficacy against Cryptococcus neoformans by blocking the fungal cell membrane
title Allicin shows antifungal efficacy against Cryptococcus neoformans by blocking the fungal cell membrane
title_full Allicin shows antifungal efficacy against Cryptococcus neoformans by blocking the fungal cell membrane
title_fullStr Allicin shows antifungal efficacy against Cryptococcus neoformans by blocking the fungal cell membrane
title_full_unstemmed Allicin shows antifungal efficacy against Cryptococcus neoformans by blocking the fungal cell membrane
title_short Allicin shows antifungal efficacy against Cryptococcus neoformans by blocking the fungal cell membrane
title_sort allicin shows antifungal efficacy against cryptococcus neoformans by blocking the fungal cell membrane
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709445/
https://www.ncbi.nlm.nih.gov/pubmed/36466672
http://dx.doi.org/10.3389/fmicb.2022.1012516
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