Gene editing tool-loaded biomimetic cationic vesicles with highly efficient bacterial internalization for in vivo eradication of pathogens
Abstract In the post-COVID-19 era, drug-resistant bacterial infections emerge as one of major death causes, where multidrug-resistant Acinetobacter baumannii (MRAB) and drug-resistant Pseudomonas aeruginosa (DRPA) represent primary pathogens. However, the classical antibiotic strategy currently face...
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| Format: | Article |
| Language: | English |
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BMC
2024-12-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-024-03065-4 |
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| author | Xueli Jia Bochuan Yuan Wanmei Wang Ke Wang Dandan Ling Meng Wei Yadan Hu Wanting Guo Ziyuan Chen Lina Du Yiguang Jin |
| author_facet | Xueli Jia Bochuan Yuan Wanmei Wang Ke Wang Dandan Ling Meng Wei Yadan Hu Wanting Guo Ziyuan Chen Lina Du Yiguang Jin |
| author_sort | Xueli Jia |
| collection | DOAJ |
| description | Abstract In the post-COVID-19 era, drug-resistant bacterial infections emerge as one of major death causes, where multidrug-resistant Acinetobacter baumannii (MRAB) and drug-resistant Pseudomonas aeruginosa (DRPA) represent primary pathogens. However, the classical antibiotic strategy currently faces the bottleneck of drug resistance. We develop an antimicrobial strategy that applies the selective delivery of CRISPR/Cas9 plasmids to pathogens with biomimetic cationic hybrid vesicles (BCVs), irrelevant to bacterial drug resistance. CRISPR/Cas9 plasmids were constructed, replicating in MRAB or DRPA and expressing ribonucleic proteins, leading to irreparable chromosomal lesions; however, delivering the negatively charged plasmids with extremely large molecular weight to the pathogens at the infection site became a huge challenge. We found that the BCVs integrating the bacterial out membrane vesicles and cationic lipids efficiently delivered the plasmids in vitro/in vivo to the pathogens followed by effective internalization. The BCVs were used by intratracheal or topical hydrogel application against MRAB pulmonary infection or DRPA wound infection, and both of the two pathogens were eradicated from the lung or the wound. CRISPR/Cas9 plasmid-loaded BCVs become a promising medication for drug-resistant bacteria infections. |
| format | Article |
| id | doaj-art-0cc6772c6bb947d48c644eebefc4f4ec |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-0cc6772c6bb947d48c644eebefc4f4ec2024-12-22T12:45:44ZengBMCJournal of Nanobiotechnology1477-31552024-12-0122112010.1186/s12951-024-03065-4Gene editing tool-loaded biomimetic cationic vesicles with highly efficient bacterial internalization for in vivo eradication of pathogensXueli Jia0Bochuan Yuan1Wanmei Wang2Ke Wang3Dandan Ling4Meng Wei5Yadan Hu6Wanting Guo7Ziyuan Chen8Lina Du9Yiguang Jin10Beijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineBeijing Institute of Radiation MedicineAbstract In the post-COVID-19 era, drug-resistant bacterial infections emerge as one of major death causes, where multidrug-resistant Acinetobacter baumannii (MRAB) and drug-resistant Pseudomonas aeruginosa (DRPA) represent primary pathogens. However, the classical antibiotic strategy currently faces the bottleneck of drug resistance. We develop an antimicrobial strategy that applies the selective delivery of CRISPR/Cas9 plasmids to pathogens with biomimetic cationic hybrid vesicles (BCVs), irrelevant to bacterial drug resistance. CRISPR/Cas9 plasmids were constructed, replicating in MRAB or DRPA and expressing ribonucleic proteins, leading to irreparable chromosomal lesions; however, delivering the negatively charged plasmids with extremely large molecular weight to the pathogens at the infection site became a huge challenge. We found that the BCVs integrating the bacterial out membrane vesicles and cationic lipids efficiently delivered the plasmids in vitro/in vivo to the pathogens followed by effective internalization. The BCVs were used by intratracheal or topical hydrogel application against MRAB pulmonary infection or DRPA wound infection, and both of the two pathogens were eradicated from the lung or the wound. CRISPR/Cas9 plasmid-loaded BCVs become a promising medication for drug-resistant bacteria infections.https://doi.org/10.1186/s12951-024-03065-4CRISPR/Cas9 plasmidOuter membrane vesicleCationic lipidAcinetobacter baumanniiPseudomonas aeruginosaPulmonary infection |
| spellingShingle | Xueli Jia Bochuan Yuan Wanmei Wang Ke Wang Dandan Ling Meng Wei Yadan Hu Wanting Guo Ziyuan Chen Lina Du Yiguang Jin Gene editing tool-loaded biomimetic cationic vesicles with highly efficient bacterial internalization for in vivo eradication of pathogens Journal of Nanobiotechnology CRISPR/Cas9 plasmid Outer membrane vesicle Cationic lipid Acinetobacter baumannii Pseudomonas aeruginosa Pulmonary infection |
| title | Gene editing tool-loaded biomimetic cationic vesicles with highly efficient bacterial internalization for in vivo eradication of pathogens |
| title_full | Gene editing tool-loaded biomimetic cationic vesicles with highly efficient bacterial internalization for in vivo eradication of pathogens |
| title_fullStr | Gene editing tool-loaded biomimetic cationic vesicles with highly efficient bacterial internalization for in vivo eradication of pathogens |
| title_full_unstemmed | Gene editing tool-loaded biomimetic cationic vesicles with highly efficient bacterial internalization for in vivo eradication of pathogens |
| title_short | Gene editing tool-loaded biomimetic cationic vesicles with highly efficient bacterial internalization for in vivo eradication of pathogens |
| title_sort | gene editing tool loaded biomimetic cationic vesicles with highly efficient bacterial internalization for in vivo eradication of pathogens |
| topic | CRISPR/Cas9 plasmid Outer membrane vesicle Cationic lipid Acinetobacter baumannii Pseudomonas aeruginosa Pulmonary infection |
| url | https://doi.org/10.1186/s12951-024-03065-4 |
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