Enantiomeric glycosylated cationic block co-beta-peptides eradicate Staphylococcus aureus biofilms and antibiotic-tolerant persisters
Year: 2019
Type: article
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.
Source: Nature Communications
Authors: Kaixi Zhang, Yu Du, Zhangyong Si, Yang Liu, Michelle E. Turvey, Cheerlavancha Raju, Damien Keogh, Lin Ruan, Subramanion L. Jothy, Sheethal Reghu, Kalisvar Marimuthu, Partha Pratim De, Oon Tek Ng, José R. Mediavilla, Barry N. Kreiswirth, Yonggui Robin Chi, Jinghua Ren, Kam C. Tam, Xue-Wei Liu, Hongwei Duan, Yabin Zhu, Yuguang Mu, Paula T. Hammond, Guillermo C. Bazan, Kevin Pethe, Mary B. Chan-Park
Institutions: Nanyang Technological University, Centre for Antimicrobial Bioengineering, Chinese Academy of Sciences, Fujian Institute of Research on the Structure of Matter, Singapore-MIT Alliance for Research and Technology, Tan Tock Seng Hospital, National Centre for Infectious Diseases, Hackensack Meridian Health, Huazhong University of Science and Technology, University of Waterloo, Ningbo University, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology, University of California, Santa Barbara
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $5,200
Award: G1816934914
OpenAlex ID: W2981229902