Enhancing the Therapeutic Potential of Peptide Antibiotics Using Bacteriophage Mimicry Strategies
Abstract The rise of antibiotic resistance, coupled with a dwindling antibiotic pipeline, presents a significant threat to public health. Consequently, there is an urgent need for novel therapeutics targeting antibiotic‐resistant pathogens. Nisin, a promising peptide antibiotic, exhibits potent bact...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202411753 |
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| author | Hongping Wan Xinyi Zhong Shinong Yang Jiarong Deng Xu Song Yong Liu Yuanfeng Li Zhongqiong Yin Xinghong Zhao |
| author_facet | Hongping Wan Xinyi Zhong Shinong Yang Jiarong Deng Xu Song Yong Liu Yuanfeng Li Zhongqiong Yin Xinghong Zhao |
| author_sort | Hongping Wan |
| collection | DOAJ |
| description | Abstract The rise of antibiotic resistance, coupled with a dwindling antibiotic pipeline, presents a significant threat to public health. Consequently, there is an urgent need for novel therapeutics targeting antibiotic‐resistant pathogens. Nisin, a promising peptide antibiotic, exhibits potent bactericidal activity through a mechanism distinct from that of clinically used antibiotics. However, its cationic nature leads to hemolysis and cytotoxicity, which has limited its clinical application. Here, nanodelivery systems have been developed by mimicking the mechanisms bacteriophages use to deliver their genomes to host bacteria. These systems utilize bacteriophage receptor‐binding proteins conjugated to loading modules, enabling efficient targeting of bacterial pathogens. Peptide antibiotics are loaded via dynamic covalent bonds, allowing for infection microenvironment‐responsive payload release. These nanodelivery systems demonstrate remarkable specificity against target pathogens and effectively localize to bacteria‐infected lungs in vivo. Notably, they significantly reduce the acute toxicity of nisin, rendering it suitable for intravenous administration. Additionally, these bacteriophage‐mimicking nanomedicines exhibit excellent therapeutic efficacy in a mouse model of MRSA‐induced pneumonia. The facile synthesis, potent antimicrobial performance, and favorable biocompatibility of these nanomedicines highlight their potential as alternative therapeutics for combating antibiotic‐resistant pathogens. This study underscores the effectiveness of bacteriophage mimicry as a strategy for transforming peptide antibiotics into viable therapeutics. |
| format | Article |
| id | doaj-art-e059216f4e414c02946e3c5922038f2f |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-e059216f4e414c02946e3c5922038f2f2025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202411753Enhancing the Therapeutic Potential of Peptide Antibiotics Using Bacteriophage Mimicry StrategiesHongping Wan0Xinyi Zhong1Shinong Yang2Jiarong Deng3Xu Song4Yong Liu5Yuanfeng Li6Zhongqiong Yin7Xinghong Zhao8Center for Sustainable Antimicrobials Department of Pharmacy, College of Veterinary Medicine Sichuan Agricultural University Chengdu 611130 ChinaCenter for Sustainable Antimicrobials Department of Pharmacy, College of Veterinary Medicine Sichuan Agricultural University Chengdu 611130 ChinaCenter for Sustainable Antimicrobials Department of Pharmacy, College of Veterinary Medicine Sichuan Agricultural University Chengdu 611130 ChinaCenter for Sustainable Antimicrobials Department of Pharmacy, College of Veterinary Medicine Sichuan Agricultural University Chengdu 611130 ChinaCenter for Sustainable Antimicrobials Department of Pharmacy, College of Veterinary Medicine Sichuan Agricultural University Chengdu 611130 ChinaState Key Laboratory of Medicinal Chemical Biology Nankai University Tianjin 300071 ChinaTranslational Medicine Laboratory The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang 325035 ChinaCenter for Sustainable Antimicrobials Department of Pharmacy, College of Veterinary Medicine Sichuan Agricultural University Chengdu 611130 ChinaCenter for Sustainable Antimicrobials Department of Pharmacy, College of Veterinary Medicine Sichuan Agricultural University Chengdu 611130 ChinaAbstract The rise of antibiotic resistance, coupled with a dwindling antibiotic pipeline, presents a significant threat to public health. Consequently, there is an urgent need for novel therapeutics targeting antibiotic‐resistant pathogens. Nisin, a promising peptide antibiotic, exhibits potent bactericidal activity through a mechanism distinct from that of clinically used antibiotics. However, its cationic nature leads to hemolysis and cytotoxicity, which has limited its clinical application. Here, nanodelivery systems have been developed by mimicking the mechanisms bacteriophages use to deliver their genomes to host bacteria. These systems utilize bacteriophage receptor‐binding proteins conjugated to loading modules, enabling efficient targeting of bacterial pathogens. Peptide antibiotics are loaded via dynamic covalent bonds, allowing for infection microenvironment‐responsive payload release. These nanodelivery systems demonstrate remarkable specificity against target pathogens and effectively localize to bacteria‐infected lungs in vivo. Notably, they significantly reduce the acute toxicity of nisin, rendering it suitable for intravenous administration. Additionally, these bacteriophage‐mimicking nanomedicines exhibit excellent therapeutic efficacy in a mouse model of MRSA‐induced pneumonia. The facile synthesis, potent antimicrobial performance, and favorable biocompatibility of these nanomedicines highlight their potential as alternative therapeutics for combating antibiotic‐resistant pathogens. This study underscores the effectiveness of bacteriophage mimicry as a strategy for transforming peptide antibiotics into viable therapeutics.https://doi.org/10.1002/advs.202411753antibiotic deliveryantibiotic resistanceantimicrobial peptidebacteriophage mimicrynanodelivery system |
| spellingShingle | Hongping Wan Xinyi Zhong Shinong Yang Jiarong Deng Xu Song Yong Liu Yuanfeng Li Zhongqiong Yin Xinghong Zhao Enhancing the Therapeutic Potential of Peptide Antibiotics Using Bacteriophage Mimicry Strategies Advanced Science antibiotic delivery antibiotic resistance antimicrobial peptide bacteriophage mimicry nanodelivery system |
| title | Enhancing the Therapeutic Potential of Peptide Antibiotics Using Bacteriophage Mimicry Strategies |
| title_full | Enhancing the Therapeutic Potential of Peptide Antibiotics Using Bacteriophage Mimicry Strategies |
| title_fullStr | Enhancing the Therapeutic Potential of Peptide Antibiotics Using Bacteriophage Mimicry Strategies |
| title_full_unstemmed | Enhancing the Therapeutic Potential of Peptide Antibiotics Using Bacteriophage Mimicry Strategies |
| title_short | Enhancing the Therapeutic Potential of Peptide Antibiotics Using Bacteriophage Mimicry Strategies |
| title_sort | enhancing the therapeutic potential of peptide antibiotics using bacteriophage mimicry strategies |
| topic | antibiotic delivery antibiotic resistance antimicrobial peptide bacteriophage mimicry nanodelivery system |
| url | https://doi.org/10.1002/advs.202411753 |
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