Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-04745-x |
| _version_ | 1797845824080707584 |
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| author | Bing Zhang Wanida Phetsang M. Rhia L. Stone Sanjaya Kc Mark S. Butler Matthew A. Cooper Alysha G. Elliott Urszula Łapińska Margaritis Voliotis Krasimira Tsaneva-Atanasova Stefano Pagliara Mark A. T. Blaskovich |
| author_facet | Bing Zhang Wanida Phetsang M. Rhia L. Stone Sanjaya Kc Mark S. Butler Matthew A. Cooper Alysha G. Elliott Urszula Łapińska Margaritis Voliotis Krasimira Tsaneva-Atanasova Stefano Pagliara Mark A. T. Blaskovich |
| author_sort | Bing Zhang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T17:45:11Z |
| format | Article |
| id | doaj.art-91aa1c2ad9ed465bac7ff7a0422f2845 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-04-09T17:45:11Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-91aa1c2ad9ed465bac7ff7a0422f28452023-04-16T11:22:40ZengNature PortfolioCommunications Biology2399-36422023-04-016111610.1038/s42003-023-04745-xSynthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damageBing Zhang0Wanida Phetsang1M. Rhia L. Stone2Sanjaya Kc3Mark S. Butler4Matthew A. Cooper5Alysha G. Elliott6Urszula Łapińska7Margaritis Voliotis8Krasimira Tsaneva-Atanasova9Stefano Pagliara10Mark A. T. Blaskovich11Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of QueenslandCentre for Superbug Solutions, Institute for Molecular Bioscience, The University of QueenslandCentre for Superbug Solutions, Institute for Molecular Bioscience, The University of QueenslandCentre for Superbug Solutions, Institute for Molecular Bioscience, The University of QueenslandCentre for Superbug Solutions, Institute for Molecular Bioscience, The University of QueenslandCentre for Superbug Solutions, Institute for Molecular Bioscience, The University of QueenslandCentre for Superbug Solutions, Institute for Molecular Bioscience, The University of QueenslandLiving Systems Institute, University of ExeterLiving Systems Institute, University of ExeterLiving Systems Institute, University of ExeterLiving Systems Institute, University of ExeterCentre for Superbug Solutions, Institute for Molecular Bioscience, The University of QueenslandAbstract 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.https://doi.org/10.1038/s42003-023-04745-x |
| spellingShingle | Bing Zhang Wanida Phetsang M. Rhia L. Stone Sanjaya Kc Mark S. Butler Matthew A. Cooper Alysha G. Elliott Urszula Łapińska Margaritis Voliotis Krasimira Tsaneva-Atanasova Stefano Pagliara Mark A. T. Blaskovich Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage Communications Biology |
| 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 |
| url | https://doi.org/10.1038/s42003-023-04745-x |
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