Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage
dc.contributor.author | Zhang, B | |
dc.contributor.author | Phetsang, W | |
dc.contributor.author | Stone, MRL | |
dc.contributor.author | Kc, S | |
dc.contributor.author | Butler, MS | |
dc.contributor.author | Cooper, MA | |
dc.contributor.author | Elliott, AG | |
dc.contributor.author | Łapińska, U | |
dc.contributor.author | Voliotis, M | |
dc.contributor.author | Tsaneva-Atanasova, K | |
dc.contributor.author | Pagliara, S | |
dc.contributor.author | Blaskovich, MAT | |
dc.date.accessioned | 2023-04-17T06:33:47Z | |
dc.date.issued | 2023-04-14 | |
dc.date.updated | 2023-04-15T11:41:01Z | |
dc.description.abstract | Antimicrobial resistance is an urgent threat to human health, and new antibacterial drugs are desperately needed, as are research tools to aid in their discovery and development. Vancomycin is a glycopeptide antibiotic that is widely used for the treatment of Gram-positive infections, such as life-threatening systemic diseases caused by methicillin-resistant Staphylococcus aureus (MRSA). Here we demonstrate that modification of vancomycin by introduction of an azide substituent provides a versatile intermediate that can undergo copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction with various alkynes to readily prepare vancomycin fluorescent probes. We describe the facile synthesis of three probes that retain similar antibacterial profiles to the parent vancomycin antibiotic. We demonstrate the versatility of these probes for the detection and visualisation of Gram-positive bacteria by a range of methods, including plate reader quantification, flow cytometry analysis, high-resolution microscopy imaging, and single cell microfluidics analysis. In parallel, we demonstrate their utility in measuring outer-membrane permeabilisation of Gram-negative bacteria. The probes are useful tools that may facilitate detection of infections and development of new antibiotics. | en_GB |
dc.description.sponsorship | Biotechnology & Biological Sciences Research Council (BBSRC) | en_GB |
dc.description.sponsorship | Engineering and Physical Sciences Research Council (EPSRC) | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | Gordon and Betty Moore Foundation | en_GB |
dc.description.sponsorship | NHMRC | en_GB |
dc.description.sponsorship | Royal Society | en_GB |
dc.description.sponsorship | China Scholarship Council (CSC) | en_GB |
dc.description.sponsorship | University of Queensland | en_GB |
dc.description.sponsorship | Institute for Molecular Biosciences | en_GB |
dc.description.sponsorship | QUEX | en_GB |
dc.description.sponsorship | GW4 | en_GB |
dc.identifier.citation | Vol. 6, article 409 | en_GB |
dc.identifier.doi | https://doi.org/10.1038/s42003-023-04745-x | |
dc.identifier.grantnumber | BB/V008021/1 | en_GB |
dc.identifier.grantnumber | EP/T017856/1 | en_GB |
dc.identifier.grantnumber | WT1104797/Z/14/Z | en_GB |
dc.identifier.grantnumber | MCPC17189 | en_GB |
dc.identifier.grantnumber | GBMF5514 | en_GB |
dc.identifier.grantnumber | APP1113719 | en_GB |
dc.identifier.grantnumber | APP2004367 | en_GB |
dc.identifier.grantnumber | APP1026922 | en_GB |
dc.identifier.grantnumber | RG180007 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/132919 | |
dc.identifier | ORCID: 0000-0001-9796-1956 (Pagliara, Stefano) | |
dc.language.iso | en | en_GB |
dc.publisher | Nature Research | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/37055536 | en_GB |
dc.rights | © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | en_GB |
dc.title | Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2023-04-17T06:33:47Z | |
exeter.article-number | 409 | |
exeter.place-of-publication | England | |
dc.description | This is the final version. Available on open access from Nature Research via the DOI in this record. | en_GB |
dc.description | All relevant data are available in this article, its Supplementary Information and Supplementary Data files (the source data behind the graphs in the paper is contained in Supplementary Data 2), except for original image files, which are available from the corresponding author upon reasonable request. | en_GB |
dc.identifier.eissn | 2399-3642 | |
dc.identifier.journal | Communications Biology | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2023-03-22 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2023-03-22 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2023-04-17T06:19:36Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2023-04-17T06:33:49Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2023-04-14 |
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Except where otherwise noted, this item's licence is described as © The Author(s) 2023. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.