Linear polymers to target Vibrio cholerae adhesion and physiology

A key stage in bacterial pathogenesis is the ability of bacteria to adhere strongly and specifically to the host. Bacterial adhesion to host cells is a prerequisite for infection and disease, and with this in mind, synthetic polymers rationally designed to incorporate side-chain functionality targeting bacterial adhesion mechanisms have been reported to cluster bacteria via specific and non-specific multivalent interactions. Targeting bacteria in this way may have therapeutic value towards controlling drug resistant pathogens. However, progress in this area has been slow due to an incomplete understanding of polymer-bacteria interactions as well as technical difficulties in screening large libraries of polymers efficiently under standardised chemical and biological conditions in order to assess structure-activity relationships of these macromolecules. Here, poly(acryloyl hydrazide) is employed as a polymer scaffold capable of undergoing highly efficient post-polymerisation modifications of the side-chain under physiologically relevant conditions to facilitate the synthesis and in situ screening of a range of unexplored polymer chemistries towards sequestering V. cholerae. In particular, it was found that imidazole-functionalised polymers dramatically sequestered V. cholerae at sub-inhibitory concentrations, and suppressed the production of the Cholera toxin (Chapter 2), while glycopolymers resulted in accelerated biofilm production in a sugar-dependent manner (Chapter 3). Lastly, improved RAFT polymerisation of poly(Boc-acryloyl hydrazide) by choice of polymerisation temperature is reported (Chapter 1), as well as a synthetic route towards controlled end group fluorescent labelling (Chapter 4)