Synergy between Synthetic Antimicrobial Polymer and Antibiotics:A Promising Platform to Combat Multidrug-resistant Bacteria

Abstract

The failure of many antibiotics in the treatment of chronic infections caused by multidrug-resistant (MDR) bacteria necessitates the development of effective strategies to combat this global healthcare issue. Here, we report an antimicrobial platform based on the synergistic action between commercially available antibiotics and a potent synthetic antimicrobial polymer that consists of three key functionalities: low-fouling oligoethylene glycol, hydrophobic ethylhexyl, and cationic primary amine groups. Checkerboard assays with Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli demonstrated synergy between our synthetic antimicrobial polymer and two antibiotics, doxycycline and colistin. Coadministration of these compounds significantly improved the bacteriostatic efficacy especially against MDR P. aeruginosa strains PA32 and PA37, where the minimal inhibitory concentrations (MICs) of polymer and antibiotics were reduced by at least 4-fold. A synergistic killing activity was observed when the antimicrobial polymer was used in combination with doxycycline, killing >99.999% of planktonic and biofilm P. aeruginosa PAO1 upon a 20 min treatment at a polymer concentration of 128 μg mL -1 (4.6 μM) and doxycycline concentration of 64 μg mL -1 (133.1 μM). In addition, this synergistic combination reduced the rate of resistance development in P. aeruginosa compared to individual compounds and was also capable of reviving susceptibility to treatment in the resistant strains.