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Designer co-beta-peptide copolymer selectively targets resistant and biofilm Gram-negative bacteria.
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.
Afiliación
  • Si Z; School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 637459, Singapore.
  • Li J; Bioinformatics Institute, A*STAR, 30 Biopolis Street, Matrix, 138671, Singapore; Singapore Eye Research Institute, 169856, Singapore.
  • Ruan L; School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 637459, Singapore.
  • Reghu S; School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 637459, Singapore.
  • Ooi YJ; School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 637459, Singapore.
  • Li P; Frontiers Science Center for Flexible Electronics, Northwestern Polytechnical University, 710072, China.
  • Zhu Y; Medical School of Ningbo University, 315211, China.
  • Hammond PT; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA; Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology (SMART) , 138602, Singapore.
  • Verma CS; Bioinformatics Institute, A*STAR, 30 Biopolis Street, Matrix, 138671, Singapore; Department of Biological Sciences, National University of Singapore, 117558, Singapore; School of Biological Sciences, Nanyang Technological University, 637551, Singapore.
  • Bazan GC; Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, 93106-9510, USA; Departments of Chemistry and Chemical & Biomolecular Engineering, National University of Singapore, 117543, Singapore. Electronic address: chmbgc@nus.edu.sg.
  • Pethe K; Lee Kong Chian School of Medicine, Nanyang Technological University, 636921, Singapore; Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, 637551, Singapore. Electronic address: kevin.pethe@ntu.edu.sg.
  • Chan-Park MB; School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 637459, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, 636921, Singapore. Electronic address: MBEChan@ntu.edu.sg.
Biomaterials ; 294: 122004, 2023 03.
Article en En | MEDLINE | ID: mdl-36669302
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Antiinfecciosos Límite: Animals Idioma: En Revista: Biomaterials Año: 2023 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Países Bajos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos / Antiinfecciosos Límite: Animals Idioma: En Revista: Biomaterials Año: 2023 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Países Bajos