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Title: Designer co-beta-peptide copolymer selectively targets resistant and biofilm Gram-negative bacteria
Authors: Si. Zhangyong
Li, Jianguo
Ruan, Lin
Reghu, Sheethal
Ooi, Ying Jie
Li, Peng
Zhu, Yabin
Hammond, Paula T.
Verma, Chandra S.
Bazan, Guillermo C.
Pethe, Kevin
Chan-Park, Mary B.
Keywords: Science::Biological sciences::Microbiology
Issue Date: 2023
Source: Si. Zhangyong, Li, J., Ruan, L., Reghu, S., Ooi, Y. J., Li, P., Zhu, Y., Hammond, P. T., Verma, C. S., Bazan, G. C., Pethe, K. & Chan-Park, M. B. (2023). Designer co-beta-peptide copolymer selectively targets resistant and biofilm Gram-negative bacteria. Biomaterials, 294, 122004-.
Project: MOE2018-T3-1-003 
Journal: Biomaterials 
Abstract: New antimicrobials are urgently needed to combat Gram-negative bacteria, particularly multi-drug resistant (MDR) and phenotypically resistant biofilm species. At present, only sequence-defined alpha-peptides (e.g. polymyxin B) can selectively target Gram-negative bacterial lipopolysaccharides. We show that a copolymer, without a defined sequence, shows good potency against MDR Gram-negative bacteria including its biofilm form. The tapered blocky co-beta-peptide with controlled N-terminal hydrophobicity (#4) has strong interaction with the Gram-negative bacterial lipopolysaccharides via its backbone through electrostatic and hydrogen bonding interactions but not the Gram-positive bacterial and mammalian cell membranes so that this copolymer is non-toxic to these two latter cell types. The new #4 co-beta-peptide selectively kills Gram-negative bacteria with low cytotoxicity both in vitro and in a mouse biofilm wound infection model. This strategy provides a new concept for the design of Gram-negative selective antimicrobial peptidomimetics against MDR and biofilm species.
ISSN: 0142-9612
DOI: 10.1016/j.biomaterials.2023.122004
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
School of Biological Sciences 
School of Chemistry, Chemical Engineering and Biotechnology 
Research Centres: Singapore Centre for Environmental Life Sciences and Engineering (SCELSE) 
Rights: © 2023 Elsevier Ltd. All rights reserved. This paper was published in Biomaterials and is made available with permission of Elsevier Ltd.
Fulltext Permission: embargo_20250207
Fulltext Availability: With Fulltext
Appears in Collections:CCEB Journal Articles
LKCMedicine Journal Articles
SBS Journal Articles
SCELSE Journal Articles

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