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Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage
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-t...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10102067/ https://www.ncbi.nlm.nih.gov/pubmed/37055536 http://dx.doi.org/10.1038/s42003-023-04745-x |
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author | Zhang, Bing Phetsang, Wanida Stone, M. Rhia L. Kc, Sanjaya Butler, Mark S. Cooper, Matthew A. Elliott, Alysha G. Łapińska, Urszula Voliotis, Margaritis Tsaneva-Atanasova, Krasimira Pagliara, Stefano Blaskovich, Mark A. T. |
author_facet | Zhang, Bing Phetsang, Wanida Stone, M. Rhia L. Kc, Sanjaya Butler, Mark S. Cooper, Matthew A. Elliott, Alysha G. Łapińska, Urszula Voliotis, Margaritis Tsaneva-Atanasova, Krasimira Pagliara, Stefano Blaskovich, Mark A. T. |
author_sort | Zhang, Bing |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10102067 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-101020672023-04-15 Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage Zhang, Bing Phetsang, Wanida Stone, M. Rhia L. Kc, Sanjaya Butler, Mark S. Cooper, Matthew A. Elliott, Alysha G. Łapińska, Urszula Voliotis, Margaritis Tsaneva-Atanasova, Krasimira Pagliara, Stefano Blaskovich, Mark A. T. Commun Biol Article 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. Nature Publishing Group UK 2023-04-14 /pmc/articles/PMC10102067/ /pubmed/37055536 http://dx.doi.org/10.1038/s42003-023-04745-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zhang, Bing Phetsang, Wanida Stone, M. Rhia L. Kc, Sanjaya Butler, Mark S. Cooper, Matthew A. Elliott, Alysha G. Łapińska, Urszula Voliotis, Margaritis Tsaneva-Atanasova, Krasimira Pagliara, Stefano Blaskovich, Mark A. T. Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage |
title | Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage |
title_full | Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage |
title_fullStr | Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage |
title_full_unstemmed | Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage |
title_short | Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage |
title_sort | synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify gram-positive bacteria, and detect gram-negative outer membrane damage |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10102067/ https://www.ncbi.nlm.nih.gov/pubmed/37055536 http://dx.doi.org/10.1038/s42003-023-04745-x |
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