Please use this identifier to cite or link to this item:
https://hdl.handle.net/10356/137198
Title: | A dual-function antibiotic-transporter conjugate exhibits superior activity in sterilizing MRSA biofilms and killing persister cells | Authors: | 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 |
Keywords: | Science::Biological sciences | Issue Date: | 2018 | Source: | 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 | Journal: | Journal of the American Chemical Society | Abstract: | 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. | URI: | https://hdl.handle.net/10356/137198 | ISSN: | 0002-7863 | DOI: | 10.1021/jacs.8b08711 | Schools: | School of Biological Sciences Interdisciplinary Graduate School (IGS) |
Research Centres: | Singapore Centre for Environmental Life Sciences and Engineering | Rights: | 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 | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | SCELSE Journal Articles |
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A dual function antibiotic-transporter.pdf | 2.46 MB | Adobe PDF | View/Open |
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