A dual-function antibiotic-transporter conjugate exhibits superior activity in sterilizing MRSA biofilms and killing persister cells
New strategies are urgently needed to target MRSA, a major global health problem and the leading cause of mortality from antibiotic-resistant infections in many countries. Here, we report a general approach to this problem exemplified by the design and synthesis of a vancomycin-d-octaarginine conjug...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2020
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| Online Access: | https://hdl.handle.net/10356/137198 |
| _version_ | 1826126236097708032 |
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| author | Antonoplis, Alexandra Zang, Xiaoyu Huttner, Melanie A. Chong, Kelvin Kian Long Lee, Yu B. Co, Julia Y. Amieva, Manuel R. Kline, Kimberly A. Wender, Paul A. Cegelski, Lynette |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Antonoplis, Alexandra Zang, Xiaoyu Huttner, Melanie A. Chong, Kelvin Kian Long Lee, Yu B. Co, Julia Y. Amieva, Manuel R. Kline, Kimberly A. Wender, Paul A. Cegelski, Lynette |
| author_sort | Antonoplis, Alexandra |
| collection | NTU |
| description | New strategies are urgently needed to target MRSA, a major global health problem and the leading cause of mortality from antibiotic-resistant infections in many countries. Here, we report a general approach to this problem exemplified by the design and synthesis of a vancomycin-d-octaarginine conjugate (V-r8) and investigation of its efficacy in addressing antibiotic-insensitive bacterial populations. V-r8 eradicated MRSA biofilm and persister cells in vitro, outperforming vancomycin by orders of magnitude. It also eliminated 97% of biofilm-associated MRSA in a murine wound infection model and displayed no acute dermal toxicity. This new dual-function conjugate displays enhanced cellular accumulation and membrane perturbation as compared to vancomycin. Based on its rapid and potent activity against biofilm and persister cells, V-r8 is a promising agent against clinical MRSA infections. |
| first_indexed | 2024-10-01T06:49:22Z |
| format | Journal Article |
| id | ntu-10356/137198 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:49:22Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1371982020-09-21T11:35:07Z A dual-function antibiotic-transporter conjugate exhibits superior activity in sterilizing MRSA biofilms and killing persister cells Antonoplis, Alexandra Zang, Xiaoyu Huttner, Melanie A. Chong, Kelvin Kian Long Lee, Yu B. Co, Julia Y. Amieva, Manuel R. Kline, Kimberly A. Wender, Paul A. Cegelski, Lynette School of Biological Sciences Interdisciplinary Graduate School (IGS) Singapore Centre for Environmental Life Sciences and Engineering Science::Biological sciences Biofilms Antimicrobial Agents New strategies are urgently needed to target MRSA, a major global health problem and the leading cause of mortality from antibiotic-resistant infections in many countries. Here, we report a general approach to this problem exemplified by the design and synthesis of a vancomycin-d-octaarginine conjugate (V-r8) and investigation of its efficacy in addressing antibiotic-insensitive bacterial populations. V-r8 eradicated MRSA biofilm and persister cells in vitro, outperforming vancomycin by orders of magnitude. It also eliminated 97% of biofilm-associated MRSA in a murine wound infection model and displayed no acute dermal toxicity. This new dual-function conjugate displays enhanced cellular accumulation and membrane perturbation as compared to vancomycin. Based on its rapid and potent activity against biofilm and persister cells, V-r8 is a promising agent against clinical MRSA infections. NMRC (Natl Medical Research Council, S’pore) Accepted version 2020-03-06T02:35:22Z 2020-03-06T02:35:22Z 2018 Journal Article Antonoplis, A., Zang, X., Huttner, M. A., Chong, K. K. L., Lee, Y. B., Co, J. Y., . . . Cegelski, L. (2018). A dual-function antibiotic-transporter conjugate exhibits superior activity in sterilizing MRSA biofilms and killing persister cells. Journal of the American Chemical Society, 140(47), 16140-16151. doi:10.1021/jacs.8b08711 0002-7863 https://hdl.handle.net/10356/137198 10.1021/jacs.8b08711 30388366 2-s2.0-85056712722 47 140 16140 16151 en Journal of the American Chemical Society This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/jacs.8b08711 application/pdf |
| spellingShingle | Science::Biological sciences Biofilms Antimicrobial Agents Antonoplis, Alexandra Zang, Xiaoyu Huttner, Melanie A. Chong, Kelvin Kian Long Lee, Yu B. Co, Julia Y. Amieva, Manuel R. Kline, Kimberly A. Wender, Paul A. Cegelski, Lynette A dual-function antibiotic-transporter conjugate exhibits superior activity in sterilizing MRSA biofilms and killing persister cells |
| title | A dual-function antibiotic-transporter conjugate exhibits superior activity in sterilizing MRSA biofilms and killing persister cells |
| title_full | A dual-function antibiotic-transporter conjugate exhibits superior activity in sterilizing MRSA biofilms and killing persister cells |
| title_fullStr | A dual-function antibiotic-transporter conjugate exhibits superior activity in sterilizing MRSA biofilms and killing persister cells |
| title_full_unstemmed | A dual-function antibiotic-transporter conjugate exhibits superior activity in sterilizing MRSA biofilms and killing persister cells |
| title_short | A dual-function antibiotic-transporter conjugate exhibits superior activity in sterilizing MRSA biofilms and killing persister cells |
| title_sort | dual function antibiotic transporter conjugate exhibits superior activity in sterilizing mrsa biofilms and killing persister cells |
| topic | Science::Biological sciences Biofilms Antimicrobial Agents |
| url | https://hdl.handle.net/10356/137198 |
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