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Antibacterial and Potentiation Properties of Charge-Optimized Polyrotaxanes for Combating Opportunistic Bacteria.

Bacteria are now becoming more resistant to most conventional antibiotics. Approaches for the treatment of multidrug-resistant bacterial infections are urgently required. Cationic polymers have broad-spectrum antibacterial activity but can also induce non-specific damage to mammalian cells. Herein, we report on the design of cationic polyrotaxanes (cPRs) with variable charge densities. cPRs were prepared by conjugating neutral ethanolamine and cationic ethylenediamine at various ratios onto threaded alpha-cyclodextrins and their antimicrobial and cytocompatible properties were investigated in vitro. In contact with Gram-negative bacteria, cPRs can disrupt the bacterial outer membrane integrity via electrostatic interactions and penetrate into the cytosol. The ability of cPRs to serve as potentiators at sub-MIC concentrations, to enhance the permeability and activity of poorly permeable antibiotics such as vancomycin, erythromycin and rifampicin, was also investigated against Gram-negative P. aeruginosa PAO1 and E. coli ATCC 25922.

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