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Herein, a hierarchical microparticle system is developed to achieve bacteria\u2010activated single\u2010 and dual\u2010antibiotic drug delivery for preventing methicillin\u2010resistant\u00a0<jats:italic>Staphylococcus aureus<\/jats:italic>\u00a0(MRSA) bacterial infections. The designed system is based on a capsosome structure, which consists of a mesoporous silica microparticle coated in alternating layers of oppositely charged polymers and antibiotic\u2010loaded liposomes. The capsosomes are engineered and shown to release their drug payloads in the presence of MRSA toxins controlled by the Agr quorum sensing system. MRSA\u2010activated single drug delivery of vancomycin and synergistic dual delivery of vancomycin together with an antibacterial peptide successfully kills MRSA\u00a0in vitro. The capability of capsosomes to selectively deliver their cargo in the presence of bacteria, producing a bactericidal effect to protect the host organism, is confirmed\u00a0in vivo\u00a0using a\u00a0<jats:italic>Drosophila melanogaster<\/jats:italic>\u00a0MRSA infection model. Thus, the capsosomes serve as a versatile multidrug, subcompartmentalized microparticle system for preventing antibiotic\u2010resistant bacterial infections, with potential applications to protect wounds or medical device implants from infections.<\/jats:p>","DOI":"10.1002\/adhm.202200036","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T09:49:14Z","timestamp":1651139354000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Bacterial Toxin\u2010Triggered Release of Antibiotics from Capsosomes Protects a Fly Model from Lethal Methicillin\u2010Resistant <i>Staphylococcus aureus<\/i> (MRSA) Infection"],"prefix":"10.1002","volume":"11","author":[{"given":"Ren\u00e9e L.","family":"Tonkin","sequence":"first","affiliation":[{"name":"Department of Materials Department of Bioengineering and Institute of Biomedical Engineering Imperial College London  London SW7 2AZ 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