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Green Fluorescent Carbon Dots as Targeting Probes for LED-Dependent Bacterial Killing

Jenny Samphire, Yuiko Takebayashi, Stephen A. Hill, Nicholas Hill, Kate J. Heesom, Philip A. Lewis, Dominic Alibhai, Eilis C. Bragginton, Josephine Dorh, Neciah Dorh, James Spencer, View ORCID ProfileM. Carmen Galan
doi: https://doi.org/10.1101/2021.03.26.437036
Jenny Samphire
1School of Chemistry, Cantock’s Close, BS8 1TS, University of Bristol
2School of Cellular & Molecular Medicine, Biomedical Sciences Building, BS8 1QU, University of Bristol
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Yuiko Takebayashi
2School of Cellular & Molecular Medicine, Biomedical Sciences Building, BS8 1QU, University of Bristol
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Stephen A. Hill
1School of Chemistry, Cantock’s Close, BS8 1TS, University of Bristol
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Nicholas Hill
2School of Cellular & Molecular Medicine, Biomedical Sciences Building, BS8 1QU, University of Bristol
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Kate J. Heesom
3Proteomics Facility, Biomedical Sciences Building, BS8 1TD, University of Bristol
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Philip A. Lewis
3Proteomics Facility, Biomedical Sciences Building, BS8 1TD, University of Bristol
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Dominic Alibhai
4Wolfson Bioimaging Facility, Biomedical Sciences Building, BS8 1QU, University of Bristol
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Eilis C. Bragginton
2School of Cellular & Molecular Medicine, Biomedical Sciences Building, BS8 1QU, University of Bristol
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Josephine Dorh
5FluoretiQ Limited, Unit DX, St Philips Central, Albert Road, BS2 0XJ, Bristol, UK
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Neciah Dorh
5FluoretiQ Limited, Unit DX, St Philips Central, Albert Road, BS2 0XJ, Bristol, UK
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James Spencer
2School of Cellular & Molecular Medicine, Biomedical Sciences Building, BS8 1QU, University of Bristol
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  • For correspondence: jim.spencer@bristol.ac.uk m.c.galan@bristol.ac.uk
M. Carmen Galan
1School of Chemistry, Cantock’s Close, BS8 1TS, University of Bristol
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  • ORCID record for M. Carmen Galan
  • For correspondence: jim.spencer@bristol.ac.uk m.c.galan@bristol.ac.uk
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ABSTRACT

The emergence of antimicrobial resistance represents a significant health and economic challenge worldwide. The slow pace of antibacterial discovery necessitates strategies for optimal use of existing agents, including effective diagnostics able to drive informed prescribing; and development of alternative therapeutic strategies that go beyond traditional small-molecule approaches. Thus, the development of novel probes able to target bacteria for detection and killing, and that can pave the way to effective theranostic strategies, is of great importance. Here we demonstrate that metal-free green-emitting fluorescent carbon dots (FCDs) synthesized from glucosamine HCl and m-phenylenediamine, and featuring 2,5-deoxyfructosazine on a robust amorphous core, can label both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) bacterial pathogens within 10 minutes of exposure. Moreover, effective killing of Gram-positive and -negative bacteria can be induced by combining FCD treatment with irradiation by LED light in the visible range. Cell-based, electron microscopy and Tandem Mass Tag (TMT) proteomic experiments indicate that FCD administration in combination with LED exposure gives rise to local heating, ROS production, and membrane- and DNA-damage, suggesting multiple routes to FCD-mediated bacterial killing. Our data identify FCDs as materials that combine facile synthesis from low-cost precursors with labelling and light-dependent killing of clinically important bacterial species, and that thus warrant further exploration as the potential bases for novel theranostics.

Competing Interest Statement

The authors have declared no competing interest.

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Green Fluorescent Carbon Dots as Targeting Probes for LED-Dependent Bacterial Killing
Jenny Samphire, Yuiko Takebayashi, Stephen A. Hill, Nicholas Hill, Kate J. Heesom, Philip A. Lewis, Dominic Alibhai, Eilis C. Bragginton, Josephine Dorh, Neciah Dorh, James Spencer, M. Carmen Galan
bioRxiv 2021.03.26.437036; doi: https://doi.org/10.1101/2021.03.26.437036
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Green Fluorescent Carbon Dots as Targeting Probes for LED-Dependent Bacterial Killing
Jenny Samphire, Yuiko Takebayashi, Stephen A. Hill, Nicholas Hill, Kate J. Heesom, Philip A. Lewis, Dominic Alibhai, Eilis C. Bragginton, Josephine Dorh, Neciah Dorh, James Spencer, M. Carmen Galan
bioRxiv 2021.03.26.437036; doi: https://doi.org/10.1101/2021.03.26.437036

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