Non-invasive in vivo sensing of bacterial implant infection using catalytically-optimised gold nanocluster-loaded liposomes for urinary readout
Staphylococcus aureus is a leading cause of nosocomial implant-associated infections, causing significant morbidity and mortality, underscoring the need for rapid, non-invasive, and cost-effective diagnostics. Here, we optimise the synthesis of renal-clearable gold nanoclusters (AuNCs) for enhanced catalytic activity with the aim of developing a sensitive colourimetric diagnostic for bacterial infection. All-atom molecular dynamics (MD) simulations confirm the stability of glutathione-coated AuNCs and surface access for peroxidase-like activity in complex physiological environments. We subsequently develop a biosensor by encapsulating these optimised AuNCs in bacterial toxin-responsive liposomes, which is extensively studied by various single-particle techniques. Upon exposure to S. aureus toxins, the liposomes rupture, releasing AuNCs that generate a colourimetric signal after kidney-mimetic filtration. The biosensor is further validated in vitro and in vivo using a hyaluronic acid (HA) hydrogel implant infection model. Urine samples collected from mice with bacteria-infected HA hydrogel implants turn blue upon substrate addition, confirming the suitability of the sensor for non-invasive detection of implant-associated infections. This platform has significant potential as a versatile, cost-effective diagnostic tool.
Authors
- Anna Klöckner (ORCID: https://orcid.org/0000-0001-9372-4144)
- Adrian Najer (ORCID: https://orcid.org/0000-0003-4868-9364)
- Leah C. Frenette (ORCID: https://orcid.org/0000-0002-0703-783X)
- David J. Peeler (ORCID: https://orcid.org/0000-0003-2441-6409)
- Patrick Charchar (ORCID: https://orcid.org/0000-0002-9201-4711)
- Chalaisorn Thanapongpibul (ORCID: https://orcid.org/0000-0002-3750-2552)
- John S. Tregoning (ORCID: https://orcid.org/0000-0001-8093-8741)
- Mohamed Chami (ORCID: https://orcid.org/0000-0002-8733-055X)
- Molly M. Stevens (ORCID: https://orcid.org/0000-0002-7335-266X)
- Colleen N. Loynachan (ORCID: https://orcid.org/0000-0001-5617-4091)
- Luca Panariello (ORCID: https://orcid.org/0000-0002-6834-5115)
- Ivan P. Parkin (ORCID: https://orcid.org/0000-0002-4072-6610)
- Kaili Chen (ORCID: https://orcid.org/0009-0005-9823-4693)
- Irene Yarovsky (ORCID: https://orcid.org/0000-0002-4033-5150)
- Kersti Karu (ORCID: https://orcid.org/0000-0002-3974-0271)
- Maria João Silva (ORCID: https://orcid.org/0000-0002-6060-0716)
- Michael Potter (ORCID: https://orcid.org/0000-0003-4688-6874)
- Andrew M. Edwards (ORCID: https://orcid.org/0000-0002-7173-7355)
- Catherine Saunders (ORCID: https://orcid.org/0009-0000-3883-9635)
- Thomas B. Clarke (ORCID: https://orcid.org/0000-0002-9997-9532)
Institutions
- King's College London (GB)
- University of Basel (CH)
- Karolinska Institutet (SE)
- University of Oxford (GB)
- MIT University (MK)
- NIHR Imperial Biomedical Research Centre (GB)
- Science Oxford (GB)
- University College London (GB)
- Imperial College London (GB)
- RMIT University (AU)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1038/s41467-024-53537-2
- Citations
- 28
- Primary Topic
- Nanocluster Synthesis and Applications
- Type
- article
- Field-Weighted Citation Impact
- 3.28
Funders
- Wellcome Trust
- Francis Crick Institute
- Australian Government
- Cancer Research UK
- Royal Academy of Engineering
- Imperial College London
- European Commission
- Rosetrees Trust
- Office of the Civil Service Commission
- Medical Research Council
- Engineering and Physical Sciences Research Council
- H2020 Marie Skłodowska-Curie Actions