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Title: Enantiomeric glycosylated cationic block co-beta-peptides eradicate Staphylococcus aureus biofilms and antibiotic-tolerant persisters
Authors: Zhang, Kaixi
Du, Yu
Si, Zhangyong
Liu, Yang
Turvey, Michelle E.
Raju, Cheerlavancha
Keogh, Damien
Ruan, Lin
Jothy, Subramanion Lachumy
Reghu, Sheethal
Marimuthu, Kalisvar
De, Partha Pratim
Ng, Oon Tek
Mediavilla, José R.
Kreiswirth, Barry N.
Chi, Robin Yonggui
Ren, Jinghua
Tam, Kam C.
Liu, Xue-Wei
Duan, Hongwei
Zhu, Yabin
Mu, Yuguang
Hammond, Paula T.
Bazan, Guillermo C.
Pethe, Kevin
Chan-Park, Mary Bee Eng
Keywords: Engineering::Chemical engineering
Issue Date: 2019
Source: Zhang, K., Du, Y., Si, Z., Liu, Y., Turvey, M. E., Raju, C., . . . Chan-Park, M. B. (2019). Enantiomeric glycosylated cationic block co-beta-peptides eradicate Staphylococcus aureus biofilms and antibiotic-tolerant persisters. Nature Communications, 10(1), 4792-. doi:10.1038/s41467-019-12702-8
Journal: Nature Communications
Abstract: The treatment of bacterial infections is hindered by the presence of biofilms and metabolically inactive persisters. Here, we report the synthesis of an enantiomeric block co-beta-peptide, poly(amido-D-glucose)-block-poly(beta-L-lysine), with high yield and purity by one-shot one-pot anionic-ring opening (co)polymerization. The co-beta-peptide is bactericidal against methicillin-resistant Staphylococcus aureus (MRSA), including replicating, biofilm and persister bacterial cells, and also disperses biofilm biomass. It is active towards community-acquired and hospital-associated MRSA strains which are resistant to multiple drugs including vancomycin and daptomycin. Its antibacterial activity is superior to that of vancomycin in MRSA mouse and human ex vivo skin infection models, with no acute in vivo toxicity in repeated dosing in mice at above therapeutic levels. The copolymer displays bacteria-activated surfactant-like properties, resulting from contact with the bacterial envelope. Our results indicate that this class of non-toxic molecule, effective against different bacterial sub-populations, has promising potential for the treatment of S. aureus infections.
ISSN: 2041-1723
DOI: 10.1038/s41467-019-12702-8
Rights: © 2019 The Author(s) (Nature Publishing Group) (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
Fulltext Permission: open
Fulltext Availability: With Fulltext
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