Polymers for binding of the gram-positive oral pathogen Streptococcus mutans

Research output: Contribution to journalArticle

Authors

  • Eugene P Magennis
  • Nora Francini
  • Francesca Mastrotto
  • Rosa Catania
  • Martin Redhead
  • David Bradshaw
  • David Churchley
  • Klaus Winzer
  • Cameron Alexander
  • Giuseppe Mantovani

Colleges, School and Institutes

External organisations

  • School of Pharmacy, University of Nottingham, Nottingham, United Kingdom.
  • School of Medicine, University of Nottingham, Nottingham, United Kingdom.
  • School of Chemistry, Haworth Building, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
  • GlaxoSmithKline, St Georges Avenue, Weybridge, Surrey, United Kingdom.
  • Clostridia Research Group, BBSRC/EPSRC Synthetic Biology Research Centre (SBRC), School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.

Abstract

Streptococcus mutans is the most significant pathogenic bacterium implicated in the formation of dental caries and, both directly and indirectly, has been associated with severe conditions such as multiple sclerosis, cerebrovascular and peripheral artery disease. Polymers able to selectively bind S. mutans and/or inhibit its adhesion to oral tissue in a non-lethal manner would offer possibilities for addressing pathogenicity without selecting for populations resistant against bactericidal agents. In the present work two libraries of 2-(dimethylamino)ethyl methacrylate (pDMAEMA)-based polymers were synthesized with various proportions of either N,N,N-trimethylethanaminium cationic- or sulfobetaine zwitterionic groups. These copolymers where initially tested as potential macromolecular ligands for S. mutans NCTC 10449, whilst Escherichia coli MG1655 was used as Gram-negative control bacteria. pDMAEMA-derived materials with high proportions of zwitterionic repeating units were found to be selective for S. mutans, in both isolated and S. mutans-E. coli mixed bacterial cultures. Fully sulfobetainized pDMAEMA was subsequently found to bind/cluster preferentially Gram-positive S. mutans and S. aureus compared to Gram negative E. coli and V. harveyi. A key initial stage of S. mutans pathogenesis involves a lectin-mediated adhesion to the tooth surface, thus the range of potential macromolecular ligands was further expanded by investigating two glycopolymers bearing α-mannopyranoside and β-galactopyranoside pendant units. Results with these polymers indicated that preferential binding to either S. mutans or E. coli can be obtained by modulating the glycosylation pattern of the chosen multivalent ligands without incurring unacceptable cytotoxicity in a model gastrointestinal cell line. Overall, our results allowed to identify a structure-property relationship for the potential antimicrobial polymers investigated, and suggest that preferential binding to Gram-positive S. mutans could be achieved by fine-tuning of the recognition elements in the polymer ligands.

Details

Original languageEnglish
Pages (from-to)e0180087
JournalPLoS ONE
Volume12
Issue number7
Publication statusPublished - 3 Jul 2017