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Antifungal Activity of ToAP2D Peptide Against Sporothrix globosa

Improving clinical efficacy and reducing treatment time have been the focus of sporotrichosis therapy. Antimicrobial peptides ToAP2A, ToAP2C, and ToAP2D were synthesized on the basis of ToAP2 (AP02759), a peptide derived from the antimicrobial peptide database by the database filtering technology, a...

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Autores principales: Yan, Tianyi, Li, Fuqiu, Li, Jinran, Chen, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566951/
https://www.ncbi.nlm.nih.gov/pubmed/34746111
http://dx.doi.org/10.3389/fbioe.2021.761518
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author Yan, Tianyi
Li, Fuqiu
Li, Jinran
Chen, Feng
author_facet Yan, Tianyi
Li, Fuqiu
Li, Jinran
Chen, Feng
author_sort Yan, Tianyi
collection PubMed
description Improving clinical efficacy and reducing treatment time have been the focus of sporotrichosis therapy. Antimicrobial peptides ToAP2A, ToAP2C, and ToAP2D were synthesized on the basis of ToAP2 (AP02759), a peptide derived from the antimicrobial peptide database by the database filtering technology, and their physicochemical characteristics were analyzed. Compared with template peptide ToAP2, the modified peptides had much shorter length, lower molecular weight but significantly greater stability, which in return resulted in increases in the aliphatic index, hydrophilicity, and protein binding ability. Here, we show that the three derived peptides inhibit the growth of Sporothrix globosa, among which ToAP2D had the strongest anti-fungal activity. ToAP2D showed good serum stability without acute toxicity. The ToAP2D treatment inhibited the growth of S. globosa and enhanced apoptosis, which was evidenced by the upregulation of apoptosis-related protein caspase-3. The scanning electron microscopy analysis revealed deformation and rupture of S. globosa. The levels of mitochondrial membrane potential were decreased and that of the reactive oxygen species (ROS) were increased in S. globosa upon ToAP2D treatment. Moreover, ToAP2D activated metacaspase. In the in vivo study, we further demonstrated that ToAP2D inhibited the S. globosa infection of mice footpads, and its efficiency was nearly comparable to itraconazole. In summary, our results suggest that antimicrobial peptide ToAP2D has the potential for sporotrichosis therapy.
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spelling pubmed-85669512021-11-05 Antifungal Activity of ToAP2D Peptide Against Sporothrix globosa Yan, Tianyi Li, Fuqiu Li, Jinran Chen, Feng Front Bioeng Biotechnol Bioengineering and Biotechnology Improving clinical efficacy and reducing treatment time have been the focus of sporotrichosis therapy. Antimicrobial peptides ToAP2A, ToAP2C, and ToAP2D were synthesized on the basis of ToAP2 (AP02759), a peptide derived from the antimicrobial peptide database by the database filtering technology, and their physicochemical characteristics were analyzed. Compared with template peptide ToAP2, the modified peptides had much shorter length, lower molecular weight but significantly greater stability, which in return resulted in increases in the aliphatic index, hydrophilicity, and protein binding ability. Here, we show that the three derived peptides inhibit the growth of Sporothrix globosa, among which ToAP2D had the strongest anti-fungal activity. ToAP2D showed good serum stability without acute toxicity. The ToAP2D treatment inhibited the growth of S. globosa and enhanced apoptosis, which was evidenced by the upregulation of apoptosis-related protein caspase-3. The scanning electron microscopy analysis revealed deformation and rupture of S. globosa. The levels of mitochondrial membrane potential were decreased and that of the reactive oxygen species (ROS) were increased in S. globosa upon ToAP2D treatment. Moreover, ToAP2D activated metacaspase. In the in vivo study, we further demonstrated that ToAP2D inhibited the S. globosa infection of mice footpads, and its efficiency was nearly comparable to itraconazole. In summary, our results suggest that antimicrobial peptide ToAP2D has the potential for sporotrichosis therapy. Frontiers Media S.A. 2021-10-21 /pmc/articles/PMC8566951/ /pubmed/34746111 http://dx.doi.org/10.3389/fbioe.2021.761518 Text en Copyright © 2021 Yan, Li, Li and Chen. 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 Bioengineering and Biotechnology
Yan, Tianyi
Li, Fuqiu
Li, Jinran
Chen, Feng
Antifungal Activity of ToAP2D Peptide Against Sporothrix globosa
title Antifungal Activity of ToAP2D Peptide Against Sporothrix globosa
title_full Antifungal Activity of ToAP2D Peptide Against Sporothrix globosa
title_fullStr Antifungal Activity of ToAP2D Peptide Against Sporothrix globosa
title_full_unstemmed Antifungal Activity of ToAP2D Peptide Against Sporothrix globosa
title_short Antifungal Activity of ToAP2D Peptide Against Sporothrix globosa
title_sort antifungal activity of toap2d peptide against sporothrix globosa
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566951/
https://www.ncbi.nlm.nih.gov/pubmed/34746111
http://dx.doi.org/10.3389/fbioe.2021.761518
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