Specifically targeted antimicrobial peptides synergize with bacterial-entrapping peptide against systemic MRSA infections
Introduction: The design of precision antimicrobials aims to personalize the treatment of drug-resistant bacterial infections and avoid host microbiota dysbiosis. Objectives: This study aimed to propose an efficient de novo design strategy to obtain specifically targeted antimicrobial peptides (STAM...
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Elsevier
2025-01-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123224000365 |
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| author | Bocheng Xu Lin Wang Chen Yang Rong Yan Pan Zhang Mingliang Jin Huahua Du Yizhen Wang |
| author_facet | Bocheng Xu Lin Wang Chen Yang Rong Yan Pan Zhang Mingliang Jin Huahua Du Yizhen Wang |
| author_sort | Bocheng Xu |
| collection | DOAJ |
| description | Introduction: The design of precision antimicrobials aims to personalize the treatment of drug-resistant bacterial infections and avoid host microbiota dysbiosis. Objectives: This study aimed to propose an efficient de novo design strategy to obtain specifically targeted antimicrobial peptides (STAMPs) against methicillin-resistant Staphylococcus aureus (MRSA). Methods: We evaluated three strategies designed to increase the selectivity of antimicrobial peptides (AMPs) for MRSA and mainly adopted an advanced hybrid peptide strategy. First, we proposed a traversal design to generate sequences, and constructed machine learning models to predict the anti-S. aureus activity levels of unknown peptides. Subsequently, six peptides were predicted to have high activity, among which, a broad-spectrum AMP (P18) was selected. Finally, the two targeting peptides from phage display libraries or lysostaphin were used to confer specific anti-S. aureus activity to P18. STAMPs were further screened out from hybrid peptides based on their in vitro and in vivo activities. Results: An advanced hybrid peptide strategy can enhance the specific and targeted properties of broad-spectrum AMPs. Among 25 assessed peptides, 10 passed in vitro tests, and two peptides containing one bacterial-entrapping peptide (BEP) and one STAMP passed an in vivo test. The lead STAMP (P18E6) disrupted MRSA cell walls and membranes, eliminated established biofilms, and exhibited desirable biocompatibility, systemic distribution and efficacy, and immunomodulatory activity in vivo. Furthermore, a bacterial-entrapping peptide (BEP, SP5) modified from P18, self-assembled into nanonetworks and rapidly entrapped MRSA. SP5 synergized with P18E6 to enhance antibacterial activity in vitro and reduced systemic MRSA infections. Conclusions: This strategy may aid in the design of STAMPs against drug-resistant strains, and BEPs can serve as powerful STAMP adjuvants. |
| format | Article |
| id | doaj-art-acac64e7d1e945fd8de3a403b636e6c0 |
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| issn | 2090-1232 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Journal of Advanced Research |
| spelling | doaj-art-acac64e7d1e945fd8de3a403b636e6c02025-08-20T02:37:06ZengElsevierJournal of Advanced Research2090-12322025-01-016730131510.1016/j.jare.2024.01.023Specifically targeted antimicrobial peptides synergize with bacterial-entrapping peptide against systemic MRSA infectionsBocheng Xu0Lin Wang1Chen Yang2Rong Yan3Pan Zhang4Mingliang Jin5Huahua Du6Yizhen Wang7National Engineering Research Center for Green Feed and Healthy Breeding, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Institute of Feed Science, Zhejiang University, Hangzhou 310058, ChinaNational Engineering Research Center for Green Feed and Healthy Breeding, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Institute of Feed Science, Zhejiang University, Hangzhou 310058, ChinaCenter for Drug Safety Evaluation and Research, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310007, ChinaNational Engineering Research Center for Green Feed and Healthy Breeding, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Institute of Feed Science, Zhejiang University, Hangzhou 310058, ChinaCollege of Animal Science, Zhejiang University, Hangzhou 310058, ChinaNational Engineering Research Center for Green Feed and Healthy Breeding, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Institute of Feed Science, Zhejiang University, Hangzhou 310058, ChinaNational Engineering Research Center for Green Feed and Healthy Breeding, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Institute of Feed Science, Zhejiang University, Hangzhou 310058, China; Corresponding authors.National Engineering Research Center for Green Feed and Healthy Breeding, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), Ministry of Agriculture and Rural Affairs, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Institute of Feed Science, Zhejiang University, Hangzhou 310058, China; Corresponding authors.Introduction: The design of precision antimicrobials aims to personalize the treatment of drug-resistant bacterial infections and avoid host microbiota dysbiosis. Objectives: This study aimed to propose an efficient de novo design strategy to obtain specifically targeted antimicrobial peptides (STAMPs) against methicillin-resistant Staphylococcus aureus (MRSA). Methods: We evaluated three strategies designed to increase the selectivity of antimicrobial peptides (AMPs) for MRSA and mainly adopted an advanced hybrid peptide strategy. First, we proposed a traversal design to generate sequences, and constructed machine learning models to predict the anti-S. aureus activity levels of unknown peptides. Subsequently, six peptides were predicted to have high activity, among which, a broad-spectrum AMP (P18) was selected. Finally, the two targeting peptides from phage display libraries or lysostaphin were used to confer specific anti-S. aureus activity to P18. STAMPs were further screened out from hybrid peptides based on their in vitro and in vivo activities. Results: An advanced hybrid peptide strategy can enhance the specific and targeted properties of broad-spectrum AMPs. Among 25 assessed peptides, 10 passed in vitro tests, and two peptides containing one bacterial-entrapping peptide (BEP) and one STAMP passed an in vivo test. The lead STAMP (P18E6) disrupted MRSA cell walls and membranes, eliminated established biofilms, and exhibited desirable biocompatibility, systemic distribution and efficacy, and immunomodulatory activity in vivo. Furthermore, a bacterial-entrapping peptide (BEP, SP5) modified from P18, self-assembled into nanonetworks and rapidly entrapped MRSA. SP5 synergized with P18E6 to enhance antibacterial activity in vitro and reduced systemic MRSA infections. Conclusions: This strategy may aid in the design of STAMPs against drug-resistant strains, and BEPs can serve as powerful STAMP adjuvants.http://www.sciencedirect.com/science/article/pii/S2090123224000365AntimicrobialsMRSA infectionsSpecifically targeted antimicrobial peptidesBacterial-entrapping peptide |
| spellingShingle | Bocheng Xu Lin Wang Chen Yang Rong Yan Pan Zhang Mingliang Jin Huahua Du Yizhen Wang Specifically targeted antimicrobial peptides synergize with bacterial-entrapping peptide against systemic MRSA infections Journal of Advanced Research Antimicrobials MRSA infections Specifically targeted antimicrobial peptides Bacterial-entrapping peptide |
| title | Specifically targeted antimicrobial peptides synergize with bacterial-entrapping peptide against systemic MRSA infections |
| title_full | Specifically targeted antimicrobial peptides synergize with bacterial-entrapping peptide against systemic MRSA infections |
| title_fullStr | Specifically targeted antimicrobial peptides synergize with bacterial-entrapping peptide against systemic MRSA infections |
| title_full_unstemmed | Specifically targeted antimicrobial peptides synergize with bacterial-entrapping peptide against systemic MRSA infections |
| title_short | Specifically targeted antimicrobial peptides synergize with bacterial-entrapping peptide against systemic MRSA infections |
| title_sort | specifically targeted antimicrobial peptides synergize with bacterial entrapping peptide against systemic mrsa infections |
| topic | Antimicrobials MRSA infections Specifically targeted antimicrobial peptides Bacterial-entrapping peptide |
| url | http://www.sciencedirect.com/science/article/pii/S2090123224000365 |
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