Bacterial Toxin-Triggered Release of Antibiotics from Capsosomes Protects a Fly Model from Lethal Methicillin-Resistant Staphylococcus aureus (MRSA) Infection.


Journal

Advanced healthcare materials
ISSN: 2192-2659
Titre abrégé: Adv Healthc Mater
Pays: Germany
ID NLM: 101581613

Informations de publication

Date de publication:
07 2022
Historique:
revised: 29 03 2022
received: 06 01 2022
pubmed: 29 4 2022
medline: 23 7 2022
entrez: 28 4 2022
Statut: ppublish

Résumé

Antibiotic resistance is a severe global health threat and hence demands rapid action to develop novel therapies, including microscale drug delivery systems. Herein, a hierarchical microparticle system is developed to achieve bacteria-activated single- and dual-antibiotic drug delivery for preventing methicillin-resistant Staphylococcus aureus (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-loaded 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-activated single drug delivery of vancomycin and synergistic dual delivery of vancomycin together with an antibacterial peptide successfully kills MRSA in 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 in vivo using a Drosophila melanogaster MRSA infection model. Thus, the capsosomes serve as a versatile multidrug, subcompartmentalized microparticle system for preventing antibiotic-resistant bacterial infections, with potential applications to protect wounds or medical device implants from infections.

Identifiants

pubmed: 35481905
doi: 10.1002/adhm.202200036
doi:

Substances chimiques

Anti-Bacterial Agents 0
Bacterial Toxins 0
Vancomycin 6Q205EH1VU

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2200036

Subventions

Organisme : Wellcome Trust
ID : 209121/Z/17/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 207467/Z/17/Z
Pays : United Kingdom

Informations de copyright

© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.

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Auteurs

Renée L Tonkin (RL)

Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.

Anna Klöckner (A)

Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, SW7 2AZ, UK.

Adrian Najer (A)

Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.

Carolina J Simoes da Silva (CJ)

MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, SW7 2AZ, UK.
Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.

Cécile Echalier (C)

Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, Oslo, 0315, Norway.

Marc S Dionne (MS)

MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, SW7 2AZ, UK.
Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.

Andrew M Edwards (AM)

MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, SW7 2AZ, UK.

Molly M Stevens (MM)

Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.

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