The Interactions between the Antimicrobial Peptide P-113 and Living <i>Candida albicans</i> 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, <i>Candida albicans</i>, the most common human fungal pathogen, may cause mucosal and even life-threatening systemic infections. P-113 (AKRHHGYKRKFH), an antimicrobial peptide (...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/7/2654 |
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| author | Kuang-Ting Cheng Chih-Lung Wu Bak-Sau Yip Ya-Han Chih Kuang-Li Peng Su-Ya Hsu Hui-Yuan Yu Jya-Wei Cheng |
| author_facet | Kuang-Ting Cheng Chih-Lung Wu Bak-Sau Yip Ya-Han Chih Kuang-Li Peng Su-Ya Hsu Hui-Yuan Yu Jya-Wei Cheng |
| author_sort | Kuang-Ting Cheng |
| collection | DOAJ |
| description | In the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients, <i>Candida albicans</i>, 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 <i>Candida albicans</i> or its degradation by <i>Candida</i>-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 <i>Candida albicans</i> 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. |
| first_indexed | 2024-03-10T20:33:00Z |
| format | Article |
| id | doaj.art-7a865c7d555c437e87676e2bea10d5ce |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:33:00Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7a865c7d555c437e87676e2bea10d5ce2023-11-19T21:16:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01217265410.3390/ijms21072654The Interactions between the Antimicrobial Peptide P-113 and Living <i>Candida albicans</i> Cells Shed Light on Mechanisms of Antifungal Activity and ResistanceKuang-Ting Cheng0Chih-Lung Wu1Bak-Sau Yip2Ya-Han Chih3Kuang-Li Peng4Su-Ya Hsu5Hui-Yuan Yu6Jya-Wei Cheng7Institute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, TaiwanInstitute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, TaiwanInstitute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, TaiwanInstitute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, TaiwanInstitute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, TaiwanInstitute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, TaiwanInstitute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, TaiwanInstitute of Biotechnology and Department of Medical Science, National Tsing Hua University, Hsinchu 300, TaiwanIn the absence of proper immunity, such as in the case of acquired immune deficiency syndrome (AIDS) patients, <i>Candida albicans</i>, 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 <i>Candida albicans</i> or its degradation by <i>Candida</i>-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 <i>Candida albicans</i> 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.https://www.mdpi.com/1422-0067/21/7/2654antimicrobial peptide<i>Candida albicans</i>proteasenon-natural amino acidNMR |
| spellingShingle | Kuang-Ting Cheng Chih-Lung Wu Bak-Sau Yip Ya-Han Chih Kuang-Li Peng Su-Ya Hsu Hui-Yuan Yu Jya-Wei Cheng The Interactions between the Antimicrobial Peptide P-113 and Living <i>Candida albicans</i> Cells Shed Light on Mechanisms of Antifungal Activity and Resistance International Journal of Molecular Sciences antimicrobial peptide <i>Candida albicans</i> protease non-natural amino acid NMR |
| title | The Interactions between the Antimicrobial Peptide P-113 and Living <i>Candida albicans</i> Cells Shed Light on Mechanisms of Antifungal Activity and Resistance |
| title_full | The Interactions between the Antimicrobial Peptide P-113 and Living <i>Candida albicans</i> Cells Shed Light on Mechanisms of Antifungal Activity and Resistance |
| title_fullStr | The Interactions between the Antimicrobial Peptide P-113 and Living <i>Candida albicans</i> Cells Shed Light on Mechanisms of Antifungal Activity and Resistance |
| title_full_unstemmed | The Interactions between the Antimicrobial Peptide P-113 and Living <i>Candida albicans</i> Cells Shed Light on Mechanisms of Antifungal Activity and Resistance |
| title_short | The Interactions between the Antimicrobial Peptide P-113 and Living <i>Candida albicans</i> Cells Shed Light on Mechanisms of Antifungal Activity and Resistance |
| title_sort | interactions between the antimicrobial peptide p 113 and living i candida albicans i cells shed light on mechanisms of antifungal activity and resistance |
| topic | antimicrobial peptide <i>Candida albicans</i> protease non-natural amino acid NMR |
| url | https://www.mdpi.com/1422-0067/21/7/2654 |
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