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The Interactions between the Antimicrobial Peptide P-113 and Living Candida albicans Cells Shed Light on Mechanisms of Antifungal Activity and Resistance
In the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients, Candida albicans, the most common human fungal pathogen, may cause mucosal and even life-threatening systemic infections. P-113 (AKRHHGYKRKFH), an antimicrobial peptide (AMP) derived from t...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178208/ https://www.ncbi.nlm.nih.gov/pubmed/32290246 http://dx.doi.org/10.3390/ijms21072654 |
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author | Cheng, Kuang-Ting Wu, Chih-Lung Yip, Bak-Sau Chih, Ya-Han Peng, Kuang-Li Hsu, Su-Ya Yu, Hui-Yuan Cheng, Jya-Wei |
author_facet | Cheng, Kuang-Ting Wu, Chih-Lung Yip, Bak-Sau Chih, Ya-Han Peng, Kuang-Li Hsu, Su-Ya Yu, Hui-Yuan Cheng, Jya-Wei |
author_sort | Cheng, Kuang-Ting |
collection | PubMed |
description | In the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients, Candida albicans, the most common human fungal pathogen, may cause mucosal and even life-threatening systemic infections. P-113 (AKRHHGYKRKFH), an antimicrobial peptide (AMP) derived from the human salivary protein histatin 5, shows good safety and efficacy profiles in gingivitis and human immunodeficiency virus (HIV) patients with oral candidiasis. However, little is known about how P-113 interacts with Candida albicans or its degradation by Candida-secreted proteases that contribute to the fungi’s resistance. Here, we use solution nuclear magnetic resonance (NMR) methods to elucidate the molecular mechanism of interactions between P-113 and living Candida albicans cells. Furthermore, we found that proteolytic cleavage of the C-terminus prevents the entry of P-113 into cells and that increasing the hydrophobicity of the peptide can significantly increase its antifungal activity. These results could help in the design of novel antimicrobial peptides that have enhanced stability in vivo and that can have potential therapeutic applications. |
format | Online Article Text |
id | pubmed-7178208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71782082020-04-28 The Interactions between the Antimicrobial Peptide P-113 and Living Candida albicans Cells Shed Light on Mechanisms of Antifungal Activity and Resistance Cheng, Kuang-Ting Wu, Chih-Lung Yip, Bak-Sau Chih, Ya-Han Peng, Kuang-Li Hsu, Su-Ya Yu, Hui-Yuan Cheng, Jya-Wei Int J Mol Sci Article In the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients, Candida albicans, the most common human fungal pathogen, may cause mucosal and even life-threatening systemic infections. P-113 (AKRHHGYKRKFH), an antimicrobial peptide (AMP) derived from the human salivary protein histatin 5, shows good safety and efficacy profiles in gingivitis and human immunodeficiency virus (HIV) patients with oral candidiasis. However, little is known about how P-113 interacts with Candida albicans or its degradation by Candida-secreted proteases that contribute to the fungi’s resistance. Here, we use solution nuclear magnetic resonance (NMR) methods to elucidate the molecular mechanism of interactions between P-113 and living Candida albicans cells. Furthermore, we found that proteolytic cleavage of the C-terminus prevents the entry of P-113 into cells and that increasing the hydrophobicity of the peptide can significantly increase its antifungal activity. These results could help in the design of novel antimicrobial peptides that have enhanced stability in vivo and that can have potential therapeutic applications. MDPI 2020-04-10 /pmc/articles/PMC7178208/ /pubmed/32290246 http://dx.doi.org/10.3390/ijms21072654 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cheng, Kuang-Ting Wu, Chih-Lung Yip, Bak-Sau Chih, Ya-Han Peng, Kuang-Li Hsu, Su-Ya Yu, Hui-Yuan Cheng, Jya-Wei The Interactions between the Antimicrobial Peptide P-113 and Living Candida albicans Cells Shed Light on Mechanisms of Antifungal Activity and Resistance |
title | The Interactions between the Antimicrobial Peptide P-113 and Living Candida albicans Cells Shed Light on Mechanisms of Antifungal Activity and Resistance |
title_full | The Interactions between the Antimicrobial Peptide P-113 and Living Candida albicans Cells Shed Light on Mechanisms of Antifungal Activity and Resistance |
title_fullStr | The Interactions between the Antimicrobial Peptide P-113 and Living Candida albicans Cells Shed Light on Mechanisms of Antifungal Activity and Resistance |
title_full_unstemmed | The Interactions between the Antimicrobial Peptide P-113 and Living Candida albicans Cells Shed Light on Mechanisms of Antifungal Activity and Resistance |
title_short | The Interactions between the Antimicrobial Peptide P-113 and Living Candida albicans Cells Shed Light on Mechanisms of Antifungal Activity and Resistance |
title_sort | interactions between the antimicrobial peptide p-113 and living candida albicans cells shed light on mechanisms of antifungal activity and resistance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178208/ https://www.ncbi.nlm.nih.gov/pubmed/32290246 http://dx.doi.org/10.3390/ijms21072654 |
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